technetium-tc-99m-tetrofosmin and Breast-Neoplasms

Following a diagnosis of breast cancer (BC), the early detection of local recurrence is important to define appropriate therapeutic strategies and increase the chances of a cure. In fact, despite major progress in surgical treatment, radiotherapy, and chemotherapy protocols, tumor recurrence is still a major problem. Moreover, the diagnosis of recurrence with conventional imaging methods can be difficult as a result of the presence of scar tissue. Molecular breast imaging (MBI) with gamma-ray emitting radiotracers may be very useful in this clinical setting, because it is not affected by the post-therapy morphologic changes. This review summarises the applications of 99mTc-sestamibi and 99mTc-tetrofosmin, the two most employed gamma emitter radiopharmaceuticals for MBI, in the diagnosis of local disease recurrence in patients with BC. The main limitation of MBI using conventional gamma-cameras is the low sensitivity for small BCs. The recent development of hybrid single photon emission computed tomography/computed tomography devices and especially of high-resolution specific breast cameras can improve the detection rate of sub-centimetric malignant lesions. Nevertheless, probably only the large availability of dedicated cameras will allow the clinical acceptance of MBI as useful complementary diagnostic technique in BC recurrence. The possible role of MBI with specific cameras in monitoring the local response of BC to neoadjuvant chemotherapy is also briefly discussed.

Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Molecular Imaging; Neoplasm Recurrence, Local; Organophosphorus Compounds; Organotechnetium Compounds; Positron-Emission Tomography; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi

Scintimammography with the cationic lipophilic (99m)Tc-tetrofosmin and (99m)Tc-methoxyisobutylisonitrile (MIBI) is one of the most widely available non-invasive imaging methods employed in the preoperative evaluation of breast cancer axillary lymph node status, for which, at present, axillary lymph node dissection (ALND) is still considered the method of choice. Comparative studies have demonstrated that single-photon emission computed tomography (SPECT) acquisition significantly improves the sensitivity and accuracy achieved with planar scintimammography, particularly when lymph nodes are non-palpable, small in size and limited in number. Thus, SPECT should be preferred to planar imaging, particularly in those patients without clinical suspicion of axillary metastatic involvement, given its high negative predictive value; however, false negative results have been reported due to the small size of lymph nodes and/or to partial or micrometastatic involvement. SPECT could also find clinical application in combination with radioguided sentinel lymph node (SLN) biopsy, providing additional useful information in selected cases. The performance of SPECT can be improved by using a pinhole collimator (pinhole SPECT), as recently demonstrated in comparative studies, and this method also determines the number of lymph nodes, thus delivering important prognostic information. Moreover, pinhole SPECT, the principal limitation of which (as with imaging methods) lies in its inability to detect micrometastases, has also proved capable of increasing the accuracy of radioguided SLN biopsy. However, only limited data relating to pinhole SPECT are available as yet, and clinical trials are necessary to validate its potential value.

Topics: Axilla; Breast Neoplasms; Cations; Humans; Lymph Nodes; Lymphatic Metastasis; Nuclear Medicine; Organophosphorus Compounds; Organotechnetium Compounds; Prognosis; Radiopharmaceuticals; Risk Assessment; Risk Factors; Sentinel Lymph Node Biopsy; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon

Non-invasive imaging methods in the evaluation of chemotherapy response in malignant tumours are currently being explored. Standard Nuclear Medicine procedures seem to offer the clinician a promising tool in the management of those oncologic patients, who might benefit from chemotherapy. Early studies focused on the relationship between radionuclides used in tumour diagnosis and factors associated with multidrug resistance (MDR). The tumour expression of P-glycoprotein (Pgp) and multidrug resistance-related protein-1 expression (MRP) have been suggested as important factors in the failure of chemotherapy. Most studies found an association between Pgp levels and (99m)Tc-sestamibi ((99m)Tc-MIBI) or (99m)Tc-Tetrofosmin uptake ((99m)Tc-TF). Currently investigations in nuclear medicine oncology are focusing on the potential role of radionuclide imaging in the assessment of chemotherapy. Recent papers discuss the usefulness of radionuclides as (99m)Tc-MIBI and (99m)Tc-TF as non-invasive procedures to predict and to monitor therapy response in patients affected by malignant tumours treatable using chemotherapy. This chapter will review the latest development in (99m)Tc-TF, giving an overview of recent investigations carried out using this radiotracer in therapy oncology, with emphasis on its potential role as predictor of tumour response.

Topics: Adult; Aged; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Drug Resistance, Multiple; Female; Humans; Lung Neoplasms; Lymphoma; Male; Melanoma; Middle Aged; Multidrug Resistance-Associated Proteins; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Treatment Failure; Treatment Outcome

Breast cancer remains one of the most common cancers in the developed world. New treatments are proving effective against both limited disease and metastases. Nuclear medicine is in a unique position as it is one of the only methods used to image the breast which is linked to cell cycle changes, the receptors on the cell surface and the cells' response to chemotherapy. Nuclear medicine is unaffected by the anatomical changes seen post-chemotherapy and radiotherapy and is uniquely placed to become a major methodology in the continued assessment of the breast cancer patient. However, before this can happen the utility of nuclear medicine techniques must be proved in multi-centre trials.

Topics: Breast Neoplasms; Female; Humans; Monitoring, Physiologic; Neoplasm Recurrence, Local; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Receptors, Estrogen; Technetium Tc 99m Sestamibi; Tissue Distribution; Tomography, Emission-Computed; Treatment Outcome

Topics: Adult; Artifacts; Axilla; Biopsy; Breast Diseases; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Drug Resistance, Multiple; Drug Resistance, Neoplasm; False Positive Reactions; Female; Forecasting; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Mammography; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Organophosphorus Compounds; Organotechnetium Compounds; Patient Selection; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate; Technetium Tc 99m Sestamibi; Thallium Radioisotopes; Ultrasonography

The wide availability and the extensive use of screening mammography have resulted in an earlier diagnosis of breast cancer and in a significant reduction in the relative risk of dying from this disease. Despite technical improvements and major advantages associated with the use of mammography (and breast ultrasound), this procedure has some limitations in clinical practice, especially in women with dense breast tissue, implants, severe dysplastic disease, or significant architectural distortion following breast surgery or radiation therapy. Different noninvasive imaging techniques have been evaluated to overcome these limitations. Nuclear medicine also has been actively involved in the detection of breast cancer, using various types of radiopharmaceuticals. Currently, there are three radiotracers commonly used for breast imaging or scintimammography in either clinical practice or research: 99mTc-sestamibi and 99mTc-tetrofosmin (two agents used for myocardial perfusion imaging) and 99mTc-MDP (methylene diphosphonate, used for bone scintigraphy). 99mTc-sestamibi was the first radiopharmaceutical to be approved by the FDA for scintimammography. Several prospective studies have shown that the overall sensitivity of 99mTc-sestamibi scintimammography in detection of breast cancer was 85%, the specificity was 89%, and the positive and negative predictive values were 89% and 84% respectively. Similar numbers have been demonstrated for 99mTc-tetrofosmin and 99mTc-MDP scintimammography. Although not indicated as a screening procedure for the detection of breast cancer, scintimammography may play a useful and significant role in various specific clinical indications such as nondiagnostic or difficult mammography, and evaluation of high-risk patients, tumor response to chemotherapy, and axillary lymph node metastatic involvement.

Topics: Breast Neoplasms; Female; Humans; Mammography; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Medronate; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

99m-Tc-tetrofosmin holds significant interest among medical oncologists because of its high positive predictive value (>90%) in pilot trials, exceeding sensitivity and specificity rates of mammography. Objective. Our objective was to assess the diagnostic accuracy of 99m-Tc-tetrofosmin whole-body scintigraphy in outpatients.. Thirty-one patients with an abnormal mammograph (n = 22) or follow-up patients (n = 9), 7 of whom were known to have metastatic disease, were included. Tracer (550 MBq) was injected into the cubital vein. Whole-body planar and single photon emission computed tomography images of regions of interest were obtained. Histology, computed tomography (CT), or magnetic resonance imaging (MRI) were performed to confirm scintigraphic results. Correlation between scintigraphy and CT or MRI was assessed by two independent radiologists. Accuracy, sensitivity, and specificity rates for the diagnosis of local and distant breast cancer lesions were given.. Of the 22 first-visit patients, 15 had breast cancer, and 7 had no evidence of any malignant disease. Of all patients examined (n = 31), 21 had distant metastases. Breast tumors were correctly diagnosed in 14/15 patients (93%), with only 1 false-negative result. Extrahepatic metastatic lesions (n = 16) were correctly diagnosed in 14 (88%) patients, whereas the method was not suitable for the diagnosis of liver metastases.. Tetrofosmin scintigraphy has shown very high detection rates of breast tumors and of metastatic lesions and is therefore a valuable option in breast cancer diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Humans; Middle Aged; Neoplasm Metastasis; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity

99mTc-Tetrofosmin (TF) is a lipophilic diphosphine compound routinely used for myocardial scintigraphy. Extracardiac utilization has occurred in evaluation of patients with malignant neoplasms and in parathyroid adenomas. Although its uptake mechanisms are not completely understood, they appear similar to those of 99mTc Setamibi (MIBI). The importance of flow and the metabolic status of cells with an intracellular uptake depending on mitochondria and the Na+/K+ pump have been hypothesized. It has also been demonstrated that Tetrofosmin shares with MIBI the property of being a substrate for P-glycoprotein (P-gp), a multidrug resistance transporter. In this review the possible clinical role in breast cancer is analysed. First experiences suggest that scintimammography with TF is useful in patients with indeterminate Mammography and to obtain complementary data to avoid surgery and/or biopsy. TF is a reliable tracer for diagnosis of primary cancer, of local recurrence of axillary lymph node metastases. Preliminary data stimulate a possible role in functional imaging of chemoresistance and in differential diagnosis of distant metastases with main reference to the evaluation of single hot lesions at bone scan.

Topics: Animals; Breast; Breast Neoplasms; Female; Humans; Mammary Neoplasms, Experimental; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Tumor Cells, Cultured

Scintimammography is a recently verified technique that will expand the use of nuclear medicine to a new group of patients in whom scintigraphic imaging has not been widely used. If performed correctly, and in certain groups of patients, it delivers a sensitivity as high as X-ray mammography or magnetic resonance imaging (MRI) in palpable tumours but with greater specificity. It is best used in patients in whom X-ray mammography, ultrasound and MRI prove non-diagnostic or unhelpful, particularly those women with dense breasts or who have had previous breast surgery. The mechanism of uptake of 99Tcm-MIBI in breast tissue is only partly understood and in itself may help in determining important aspects of tumour function, such as the response to cytotoxic chemotherapy. Other scintigraphic methods for imaging breast cancer may be able to look at other aspects of cancer function, for example blood supply, metabolic rate or the in vivo assessment of oestrogen or somatostatin receptor status. This in turn may be useful in planning treatment. Metastatic disease may best be monitored with 18F-FDG PET, which has a sensitivity greater than MRI but a similar specificity. Much furtner work will need to be done on the use of nuclear medicine in breast cancer, but the addition of unique functional information to the anatomical data from X-ray and MRI should benefit future patients' management.

Topics: Breast Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Neoplasm Staging; Organophosphorus Compounds; Organotechnetium Compounds; Receptors, Estrogen; Receptors, Somatostatin; Reproducibility of Results; Technetium Tc 99m Sestamibi; Thallium; Thallium Radioisotopes; Tomography, Emission-Computed

We evaluated the usefulness of (99m)Tc-tetrofosmin axillary pinhole (P)-SPECT in breast cancer (BC) non palpable axillary lymph node metastasis detection compared with conventional planar and SPECT scintimammography.. We studied prospectively 188 consecutive patients with suspected primary BC, negative at axillary clinical examination. Ten minutes after 740 MBq (99m)Tc-tetrofosmin injection, planar and SPECT scintimammography were acquired, followed by axillary P-SPECT imaging.. At histology, 12 patients had benign mammary lesions and 176 had BC. Axillary lymph node dissection (ALND) was performed in all BC patients, bilaterally in 3 cases: 74/179 axillae had metastases. P-SPECT showed a significantly higher overall sensitivity than SPECT and planar (93.2% vs 85.1% and 36.5%, respectively; p<0.05 and p<0.0005, respectively) and was false negative in 5 patients with 1 metastatic node each, micrometastatic in 4/5 cases; SPECT and planar were also false negative in these 5 cases and in 6 and in 42 further cases, respectively. P-SPECT added important prognostic information by distinguishing single from multiple and pound 3 from >3 nodes; only P-SPECT defined the exact number of nodes in 15/25 patients with 2-4 nodes. P-SPECT showed the highest accuracy and NPV: 92.7% and 95%, respectively (SPECT 90.5% and 90%, respectively; planar 73.2% and 68.9%, respectively).. (99m)Tc-tetrofosmin axillary P-SPECT appears highly accurate in BC non palpable axillary lymph node metastasis detection and significantly more sensitive than both planar and SPECT, its few false negative results predominantly concerning micrometastases; moreover, only P-SPECT gave additional important prognostic information. Given its very high NPV, P-SPECT could also be used to better select patients who might avoid ALND.

Topics: Adult; Aged; Axilla; Breast Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Palpation; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Scintimammography using 99Tc(m)-MIBI (99Tc(m)-sestamibi) has demonstrated promising results in the detection of breast cancer. Recently scintimammography using 99Tc(m)-tetrofosmin has been suggested as a better diagnostic tool and a more convenient agent to use in this condition. In this study we compared both agents in 35 consecutive women with abnormal mammographic or physical findings. Thirty-four of them underwent MIBI scan, followed by tetrofosmin scan 2 days later (performed on all 35 women). Within 2 weeks, a pathological diagnosis was obtained either by needle or open biopsy. In both scans the uptake ratio between the lesion and the background uptake was calculated. Twenty patients who underwent tetrofosmin scan and 19 patients with MIBI scan had malignant breast tumours, while 15 women had benign lesions. The sensitivity, specificity, positive and negative predictive values and total accuracy of the MIBI scan were 89.4%, 80%, 85%, 85.7% and 85.3%, respectively; almost identical values were obtained with tetrofosmin (90%, 80%, 85.6%, 85.7% and 85.7%, respectively). The uptake ratios in the MIBI and tetrofosmin scans were 1.68 +/- 0.52 and 1.7 +/- 0.47, respectively. No differences were found between the two scintimammographies in all the parameters examined. In conclusion, MIBI and tetrofosmin breast scans are accurate and equally efficient for the detection of breast malignancies.

Topics: Adult; Aged; Breast Neoplasms; Female; Humans; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi

99m-Tc-tetrofosmin holds significant interest among medical oncologists because of its high positive predictive value (>90%) in pilot trials, exceeding sensitivity and specificity rates of mammography. Objective. Our objective was to assess the diagnostic accuracy of 99m-Tc-tetrofosmin whole-body scintigraphy in outpatients.. Thirty-one patients with an abnormal mammograph (n = 22) or follow-up patients (n = 9), 7 of whom were known to have metastatic disease, were included. Tracer (550 MBq) was injected into the cubital vein. Whole-body planar and single photon emission computed tomography images of regions of interest were obtained. Histology, computed tomography (CT), or magnetic resonance imaging (MRI) were performed to confirm scintigraphic results. Correlation between scintigraphy and CT or MRI was assessed by two independent radiologists. Accuracy, sensitivity, and specificity rates for the diagnosis of local and distant breast cancer lesions were given.. Of the 22 first-visit patients, 15 had breast cancer, and 7 had no evidence of any malignant disease. Of all patients examined (n = 31), 21 had distant metastases. Breast tumors were correctly diagnosed in 14/15 patients (93%), with only 1 false-negative result. Extrahepatic metastatic lesions (n = 16) were correctly diagnosed in 14 (88%) patients, whereas the method was not suitable for the diagnosis of liver metastases.. Tetrofosmin scintigraphy has shown very high detection rates of breast tumors and of metastatic lesions and is therefore a valuable option in breast cancer diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Humans; Middle Aged; Neoplasm Metastasis; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity

A reduction in acquisition times from 10 to 5 min for scintimammography does not reduce the diagnostic value of the study when imaging for detection of breast lesions. The test showed an overall sensitivity of 96%, specificity of 100% and accuracy of 98% for breast lesions visualized on both 5 and 10 min acquisitions. Even if lymph node detection is the primary concern of the study, longer scan times do not increase the sensitivity of the test (40% on both 5 and 10 min). Scintimammography is poor at detecting lymph nodes (sensitivity 40%, specificity 69-82%) and is not useful for assessing lymph node involvement. A reduction in imaging times appeared to be consistent on both camera systems tested, which have very different display outputs. This would indicate that other departments may be able to reduce times on their systems without affecting the quality of the study. The detection of breast lesions was also consistent between reporters.

Topics: Breast; Breast Neoplasms; Female; Humans; Lymph Node Excision; Mammography; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Time Factors

The aim of this study was to assess the diagnostic value of technetium-99m-tetrofosmin and technetium-99m-MIBI in a head-to-head comparison. Both radiopharmaceuticals are routinely used for detecting breast cancer. In a prospective, open, diagnostic trial, the two radiopharmaceuticals were administered randomly on different days to the same 101 women suffering from 103 breast tumours. Planar images and single photon emission computer tomography (SPET) were performed. After histological examination of the tumours, sensitivity, specificity and positive and negative predictive value were compared. 99mTc-tetrofosmin and 99mTc-MIBI showed low sensitivity in planar images (44% vs 46%, respectively). SPET improved sensitivity (70% vs 69%, respectively). Specificity in planar images was 83% and 87%, and it was even lower using SPET (70% vs 78%, respectively). Positive predictive value in planar images was 76% vs 81%, and it was not changed by SPET. Negative predictive value was low in planar images (54% vs 57%, respectively), but it was improved by using SPET (65% vs 67%, respectively). In conclusion, 99mTc-tetrofosmin and 99mTc-MIBI scintigraphy show similar diagnostic value in assessing suspicious breast lesions.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi

To investigate the use of Tc-99m tetrofosmin as a breast imaging agent and to compare results of Tc-99m tetrofosmin scintimammography with plain-film mammography and pathological outcome.. Forty-four patients (mean age, 51 years; range 26-79 years) with a palpable breast mass requiring fine needle aspiration biopsy (FNAB) were prospectively studied. All patients had Tc-99m tetrofosmin scintimammography. Patients over 35 years of age had two view mammography performed on the same day. FNAB was performed within 2 weeks of imaging, and patients referred for surgery as appropriate. Results of scintigraphy and plain-film mammography were correlated with pathological outcome.. Of the 44 patients, 21 had biopsy proven malignancy while 23 had benign lesions. Of the 21 patients with carcinoma, 20 (95.2%) had positive Tc-99m tetrofosmin scintimammography while 21 (91.3%) of the 23 patients with benign histology had negative scintigraphy. The sensitivity of scintimammography was 95.24%, the specificity was 91.3%, with a positive predictive value of 90.9% and a negative predictive value of 95.45%. Thirty-eight patients had two view mammography performed (six patients were <35 years of age). Of these 38 patients, 21 had biopsy proven malignancy while 17 had benign histology (all patients <35 years of age had benign histology). Of the 21 patients with malignancy, plain-film mammography was suspicious for malignancy in 17 (81%) while four were reported as benign. Of the 17 with benign disease, 14 patients (82.4%) had benign appearances on plain-film mammography while three (18%) had one or more findings suspicious for malignancy. The sensitivity of plain-film mammography in our group was 81%, with a specificity of 82.4%, a positive predictive value of 85% and a negative predictive value of 77.8%. Tc-99m tetrofosmin scintimammography correctly characterized all seven lesions where mammographic evaluation was limited because of dense breast parenchyma or previous surgery and/or radiotherapy.. Tc-99m tetrofosmin scintimammography is an accurate, well tolerated and non-invasive method of differentiating benign from malignant palpable breast lesions. Negative Tc-99m tetrofosmin scintimammography excludes malignancy with a high degree of confidence while false-positive scintigraphy can occur in cases of proliferative dysplasia and hypercellular fibroadenoma. Tc-99m tetrofosmin scintimammography is particularly useful when plain-film mammography is indeterminate or limited in patients with dense breasts or a history of previous surgery and/or radiotherapy.

Topics: Adult; Aged; Biopsy, Needle; Breast Neoplasms; Female; Follow-Up Studies; Humans; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Palpation; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity

Eighty-five women, 18 to 80 years of age, with palpable breast lumps were studied 1-4 days before surgery in order to evaluate 99mTc Tetrofosmin imaging for the detection of malignant breast tumours. Intravenous injection of 99mTc Tetrofosmin was followed by 3 min planar images at 5-60 min postinjection. In the latter 57 patients, planar imaging was preceded by a dynamic study of 20x5 sec images. The myocardium was always included in the field of the left breast. Count rates in suspicious areas were compared with normal tissue areas in the same and the opposite breast and with myocardial counts. Data analysis showed that 77 of the 85 scan results were in agreement with the histological findings; six scans were false negative and two false positive for malignancy. The sensitivity of the method was 90.32% and the specificity 91.30%, with a positive predictive value of 96.55%. We conclude that breast scanning with 99mTc Tetrofosmin may play an important role in the detection of breast malignancies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Humans; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Pilot Projects; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity

Topics: Artifacts; Breast; Breast Neoplasms; Coronary Artery Disease; False Positive Reactions; Female; Humans; Image Processing, Computer-Assisted; Male; Myocardial Perfusion Imaging; Organophosphorus Compounds; Organotechnetium Compounds; Phantoms, Imaging; Prognosis; Reproducibility of Results; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon

Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer. The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density (MVD), Doppler sonography (DS) and 99mTc-Tetrofosmin (TF) uptake. Ehrlich ascites tumour cell xenografts, Pgp-negative tumour were divided into two groups: (a) Morphine sulphate [0.714 mg/kg/day (equivalent to 50 mg per day for a 70 kg human)], (b) no-morphine. For the determination of angiogenesis in mice tumour tissue, TF scintigraphy, microvessel density and DS were done. MVD was significantly different between groups (49.4±1.8 vs. 41.8±1.9, morphine and no-morphine groups, respectively, P<0.001). A strong correlation was found between late uptakes of mass at scintigraphy and degree of angiogenesis in histopathologic examination (r=0.52, P<0.01). There was statistically significant inverse correlation between degree of angiogenesis in histopathologic examination and washout ratio of TF (r=0.40, P<0.05). The higher values for angiogenesis are related to higher TF reuptake. There was no statistically significant correlation between DS and TF. A strong correlation was found between MVD and grade of DS (r=0.51, P<0.01). Our preclinical mice study indicates that morphine at clinically relevant doses stimulates angiogenesis, and angiogenesis triggered of morphine is demonstrated with MVD and DS, but not TF. However, uptake and washout of TF are compared with immunohistochemically assessed morphine-stimulated angiogenesis in tumour tissue.

Topics: Animals; Breast Neoplasms; Carcinoma, Ehrlich Tumor; Disease Models, Animal; Female; Immunohistochemistry; Mice; Mice, Inbred BALB C; Morphine; Narcotics; Neovascularization, Pathologic; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Ultrasonography, Doppler

Single photon emission computed tomography (SPECT)/CT is emerging as a useful diagnostic tool in several oncological fields. In this prospective study, we assessed the usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of both residual breast tumors and axillary lymph node metastases following neoadjuvant therapy. Thirty-seven consecutive breast cancer patients scheduled to surgery following neoadjuvant therapy preoperatively underwent a Tc-99m-tetrofosmin SPECT/CT study, using a dual head gamma camera integrated with a x-ray tube for low-dose CT, including both breasts and axillary regions in the field of view. Within 1 week of SPECT/CT, all 37 patients had breast surgery with associated axillary lymph node dissection in 33/37 cases. At surgery, 31/37 patients had breast residues (microscopic in 4/31 cases and macroscopic in 27/31 cases). Axillary lymph node metastases were ascertained in 19/33 cases (N1mi: 2 cases, N1a: 8 cases, N2a: 6 cases, N2b: 3 cases). SPECT/CT sensitivity, specificity, and accuracy in detecting residual tumors were 87%, 100%, and 89.2%, respectively; the corresponding values in detecting axillary lymph node metastases were 36.8%, 92.8%, and 60.6%. SPECT/CT missed breast cancer residues in 4/31 patients, including 2 cases with microscopic residual disease. Moreover, lymph node metastases were missed in 12/19 patients (10/12 with pN1mi or pN1a metastases), all with lymph nodes with post-therapy fibrotic changes and small deposits of metastases. Tc-99m-tetrofosmin SPECT/CT proved a useful diagnostic tool in the detection and in the localization of residual breast tumors following neoadjuvant therapy. The procedure lacked in sensitivity in identifying axillary lymph node metastases, especially in patients with a limited lymph node involvement. According to our data, SPECT/CT may guide the surgeon to the most appropriate breast surgical treatment and to eventually select the most suitable axillary lymph node sampling (axillary lymph node dissection or sentinel node biopsy).

Topics: Adult; Aged; Aged, 80 and over; Axilla; Breast Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm, Residual; Organophosphorus Compounds; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

To evaluate the cardiac toxicity of radiotherapy (RT) in breast cancer (BC) patients employing myocardial perfusion imaging (MPI) with Tc-99 m Tetrofosmin-single photon emission computer tomography (T-SPECT).. We studied 46 BC female patients (28 patients with left and 18 patients with right BC) treated with postoperative RT compared to a control group of 85 age-matched females. The median time of RT to SPECT was 40 months (6-263).. Abnormalities in the summed stress score (SSS) were found in 54% of left BC patients, 44.4% of right BC patients, and 32.9% of controls. In left BC patients there were significantly more SSS abnormalities compared to controls (4.0 ± 3.5 vs 2.6 ± 2.0, p = 0.05) and possible trend of increased abnormalities of right BC patients (3.7 ± 3.0 vs 2.6 ± 2.0, p = 0.14). Multiple regression analysis showed more abnormalities in the MPI of left BC patients compared to controls (SSS, p = 0.0001); Marginal toxicity was also noted in right BC patients (SSS, p = 0.045). No additional toxicity was found in patients that received adjuvant cardiotoxic chemotherapy. All T-SPECT abnormalities were clinically silent.. The study suggests that radiation therapy to BC patients result in MPI abnormalities but without apparent clinical consequences.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Case-Control Studies; Chemotherapy, Adjuvant; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Postoperative Period; Radiopharmaceuticals; Radiotherapy; Risk Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

This study was done to examine the effect of asiaticoside on MCF-7 cell uptake of (99m)Tc-tetrofosmin ((99m)Tc-Tfos) and (99m)Tc-sestamibi ((99m)Tc-MIBI).. The 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the effect of a 50% inhibitory concentration of asiaticoside on MCF-7 cell proliferation. MCF-7 cells were treated with 10, 20, 30, 40, and 50 μM asiaticoside for 48 h and then incubated with 59.2 MBq of either (99m)Tc-Tfos or (99m)Tc-MIBI tracer for 60 min. The uptake of the tracers was measured with a dose calibrator.. The 50% inhibitory concentration of asiaticoside for MCF-7 cells was determined with the MTT assay to be 40 μM. The uptake results were expressed as the mean ± SE radioactivity in MBq/mg of protein, and P values were also calculated (P values of 0.03 indicated significant differences). In the control (no asiaticoside) and at 10, 20, 30, 40, and 50 μM asiaticoside, the mean levels of (99m)Tc-Tfos uptake were 0.79 (SE, 0.059) (P = 0.14), 0.84 (SE, 0.057) (P = 0.60), 0.47 (SE, 0.034) (P = 0.03), 0.40 (SE, 0.050) (P = 0.03), 0.37 (SE, 0.050) (P = 0.03), and 0.15 (SE, 0.023) (P = 0.03), respectively; the mean levels of (99m)Tc-MIBI uptake were 0.95 (SE, 0.007) (P = 0.14), 0.81 (SE, 0.009) (P = 0.60), 0.79 (SE, 0.019) (P = 0.03), 0.63 (SE, 0.004) (P = 0.03), 0.13 (SE, 0.006) (P = 0.03), and 0.07 (SE, 0.008) (P = 0.03), respectively. Asiaticoside concentrations of 10, 20, 30, 40, and 50 μM revealed the uptake kinetics for both (99m)Tc-Tfos and (99m)Tc-MIBI in MCF-7 cells. (99m)Tc-Tfos and (99m)Tc-MIBI showed similar trends; the radioactivity uptake was dose dependent, and asiaticoside inhibited 16% and 47% of (99m)Tc-Tfos uptake and (99m)Tc-MIBI uptake in MCF-7 cells, respectively.. This study showed that asiaticoside, acting as a biochemical modulator, may induce apoptosis and enhance antitumor activity in MCF-7 cells, as determined by (99m)Tc-Tfos and (99m)Tc-MIBI uptake. These findings are promising for cancer chemotherapy. Future studies should be performed to confirm our findings and to further delineate the clinical role of asiaticoside.

Topics: Anti-Infective Agents; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Metabolic Clearance Rate; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Triterpenes

Planar scintimammography (SM) acquired with a conventional gamma camera has proved a useful complementary tool to mammography (Mx) in breast cancer (BC) diagnosis, but with unsatisfactory sensitivity in small size carcinomas. In this study we assessed the role of planar SM with a high-resolution dedicated breast camera (DBC) in BC diagnosis, comparing the results with those of Mx.A consecutive series of 145 patients scheduled for biopsy for suspected BC underwent Tc-99m tetrofosmin planar SM using a newly developed DBC. Scintigraphic data were compared with Mx findings and correlated to histology.Histopathologic analysis revealed 165 lesions: 143 malignant and 22 benign. SM detected 139/143 carcinomas (overall sensitivity: 97.2%) and was true negative in 19/22 benign lesions (overall specificity: 86.4%). SM sensitivity was 91% in < or =10-mm carcinomas. SM was more accurate than Mx in 42/145 cases (29%), detecting cancer in 9 patients with Mx indeterminate for dense breasts (8/9 tumors were <10 mm), assessing additional tumor foci (all <10 mm) in 5 points with multifocal disease and correctly classifying 28 patients with inconclusive mammographic findings as affected by cancer or by benign disease. Mx was more accurate than SM in 3 patients, in each detecting 1 subcentimeter BC false negative on SM.DBC planar SM seems a highly sensitive diagnostic tool in the detection of BC, even when small in size, and in the assessment of multifocal disease. A wider employment of this procedure is thus suggested, especially in indeterminate or inconclusive mammographic findings to improve sensitivity and specificity of Mx.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Gamma Cameras; Humans; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity

The aim of the current study was to compare the diagnostic reliability of visual and quantitative indices of double phase Tc-99m MIBI scintimammography (M-SMM) and Tc-99m Tetrofosmin scintimammography (TF-SMM) for detection of breast cancer. Double phase M-SMM and TF-SMM (early; 10 minutes, delayed; hour) were performed after injection of 925 MBq of radiotracers in 75 highly suspected breast cancer patients (malignant:49, benign:26). For visual analysis, five scoring methods were used. For quantitative analysis, early, delayed lesions to non-lesion ratios (L/Ns), and washout rate (%, WR) were calculated. When over grade of visual grade was used as cut-off value in the detection of primary breast cancer, M-SMM and TF-SMM showed similar diagnostic accuracies. The optimal quantitative indices of M-SMM for the detection of breast cancer were 2.06 for early L/N and 1.72 for delayed L/N. Those of TF-SMM were 3.13 for early, and 2.56 for delayed image. Visual and quantitative analyses showed similar results. However, delayed L/N of M-SMM was superior to that of TF-SMM for the detection of breast cancer. In conclusion, the double phase M-SMM and TF-SMM showed favorable diagnostic accuracy in differentiating benign from malignant breast lesions, visually and quantitatively. The optimal visual interpretation grades for the detection of primary breast cancer of double phase M-SMM and TF-SMM were grade and 5. The optimal quantitative indices of M-SMM for the detection of breast cancer were 2.06 for early L/N and 1.72 for delayed L/N. Those of TF-SMM were 3.13 for early, and 2.56 for delayed image.

Topics: Breast Neoplasms; Female; Humans; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Technetium Tc 99m Sestamibi

To assess the clinical value of (99m)Tc-tetrofosmin ((99m)Tc-TF) planar and single-photon emission computed tomography (SPECT) in comparison with ultrasonography in the diagnosis of breast cancer.. Fifty women underwent (99m)Tc-TF planar imaging, SPECT and ultrasonographic examinations, and with the results of histopathological examination as the golden standard, the diagnostic value of the 3 modalities were compared in the detection of malignancies of the breast neoplasms.. The sensitivity of planar imaging, SPECT and ultrasonography in breast cancer diagnosis was 74.2%, 93.5%, and 87.1%, with specificity of 66.7%, 77.3%, and 80.0%, respectively.. (99m)Tc-TF imaging is a new and effective method for diagnosis of breast cancer.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Ultrasonography, Mammary

Conventional imaging procedures have proved of limited value in assessing tumor response to neoadjuvant chemotherapy in locally advanced primary breast cancer (LAPBC). We evaluated the usefulness of radioisotopic procedures comparing planar scintimammography (SM) to SPECT, monitoring pre-surgery neoadjuvant chemo- or hormonotherapy response in 32 LAPBC patients. In all cases, 99mTc-tetrofosmin conventional planar SM and SPECT were acquired by dual-head gamma camera with HR parallel hole collimators. In 15 cases, planar SM with small field of view high resolution dedicated breast camera (DBC) was also acquired. Scintigraphic data always correlated with histopathological findings. At surgery, 4/32 patients had pathological complete remission (pCR), while 28/32 patients had residual tumors. Both conventional planar SM and SPECT were true negative in 4/4 (100%) pCR patients, as was DBC in the only studied case. Conventional planar SM and SPECT detected residual tumors in 23/28 (82%) and in 25/28 (89.2%) cases, respectively. Both procedures missed 2 multifocal, scattered microscopic residues, only evidenced at DBC. Conventional planar SM also missed 3 further macroscopic residues (15-20 mm), while SPECT only one of these, a mucinous BC, in which DBC was not performed. DBC correctly classified all other 12 patients in whom the procedure was performed. Both conventional planar SM and SPECT proved useful diagnostic tools in monitoring neoadjuvant chemo/hormono therapy response in LAPBC with SPECT appearing more sensitive; however, our data, although in a limited number of cases, suggest that sensitivity can further be increased using high resolution DBC, especially in detecting microscopic residual tumor foci.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Androstadienes; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Humans; Lymph Nodes; Mammography; Mass Screening; Middle Aged; Neoadjuvant Therapy; Organophosphorus Compounds; Organotechnetium Compounds; Prognosis; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

The aim of this study was to assess the usefulness of planar scintimammography (SM) with a high-resolution dedicated breast camera (DBC) compared to SPECT in unifocal and multifocal/multicentric primary breast cancer (BC) detection. DBC planar SM and conventional SPECT were acquired using 99mTc-tetrofosmin as radiotracer in 85 consecutive patients suspect for BC at conventional imaging and clinical examination. Scintigraphic data were related to histology in all cases. BC was proven in 74/85 patients, unifocal in 56/74 cases and multifocal/multicentric in 18/74; 90 carcinomas were ascertained. Benign lesions were found in 12 cases, including one who also had BC in the contralateral breast. DBC planar SM and SPECT were true-positive in 72/74 and in 70/74 BC patients, respectively, and globally detected 96.7% and 92.2% of carcinomas. DBC and SPECT sensitivity were, respectively, 90.3% and 80.6% in

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; False Positive Reactions; Female; Humans; Mammography; Mass Screening; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

We evaluated the predictive value of bone marrow accumulation of technetium (Tc)-99m tetrofosmin in patients with breast cancer for distant metastases in comparison with conventional prognostic factors such as clinical stage, tumor size, axillary lymph node (Node) status, and estrogen receptor (ER) status.. Bone marrow scans with Tc-99m tetrofosmin were performed on 64 patients with breast cancer who had no clinical evidence of distant metastases. Accumulation in the femoral marrow was classified into four patterns, no detectable, lower, higher, and intensively higher. Higher or intensively higher pattern was interpreted as abnormal. Thirty-six patients with abnormal accumulation (marrow-positive group) and 28 patients without abnormal accumulation (marrow-negative group) were enrolled in the follow-up study. The mean length of observation after scans was approximately 3 years. The predictive value of femoral marrow status and conventional prognostic factors for distant metastases was evaluated by statistical analysis.. Univariate analysis showed a significantly higher incidence of subsequent bone metastases (36%>4%; P<0.005), and distant metastases (69%>18%; P<0.001) in the marrow-positive group when compared with the marrow-negative group. Conventional prognostic factors except tumor size were also significantly associated with the development of distant metastases; 77% in clinical stage 3>39% in clinical stages 1, 2, P<0.05; 64% in Node-positive>29% in Node-negative, P<0.01; and 70% in ER negative>27% in ER positive, P<0.005. These conventional factors were not significantly associated with bone metastases. The Cox proportional hazard ratio for bone metastases was markedly higher in femoral marrow status (hazard ratio=11.07). The distant metastases-free survival was significantly reduced in ER negative (P<0.0005), Node-positive (P=0.0215), and clinical stage 3 patients (P=0.0163). On the other hand, a more marked difference was observed in the femoral marrow status (P<0.0001). The hazard ratio for distant metastases was 2.44 in clinical stage, 2.74 in tumor size, 2.74 in Node, and 3.68 in ER, which were each independent prognostic factors associated with distant metastases. However, femoral marrow status was markedly associated with distant metastases (hazard ratio=5.27).. Bone marrow accumulation of Tc-99m tetrofosmin can be a promising prognostic factor independent of conventional prognostic factors for predicting development of not only bone metastases but also distant metastases in breast cancer.

Topics: Adult; Aged; Aged, 80 and over; Bone Marrow; Breast Neoplasms; Female; Femoral Neoplasms; Humans; Lymphatic Metastasis; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity

We evaluated the usefulness of (99m)Tc-tetrofosmin planar scintigraphy acquired with a high-resolution (HR) dedicated breast camera in comparison with conventional single-photon emission computed tomography (SPECT) and pinhole-SPECT (P-SPECT) in breast cancer (BC) axillary lymph node metastasis detection in a consecutive series of 76 BC patients, 28 of whom had axillary lymph node metastases, including 9 positive at clinical examination. HR planar scintigraphy was true positive in only 7 patients with >3 palpable metastases (sensitivity: 25%), while SPECT was true positive in 23 of 28 cases (sensitivity: 82.1%) and P-SPECT in 25 of 28 (sensitivity: 89.3%). SPECT was false negative in 5 patients with nonpalpable 3 metastatic nodes. SPECT should be preferred, significantly improving the sensitivity of planar scintigraphy, especially when using a pinhole collimator.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Gamma Cameras; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

To compare the diagnostic performances of visual and quantitative indices of double phase Tc-99m Tetrofosmin scintimammography (TF-SMM) for the detection of breast cancer.. Double phase TF-SMM (early, 10 min; delayed, 3h) were performed after injection of 925 MBq of Tc-99m Tetrofosmin in 75 highly suspected breast cancer patients (malignant: 49, benign: 26). For visual analysis, five scoring method was used. For quantitative analysis, early, delayed lesions to non-lesion ratios (L/Ns) and washout rate (%, WR) were calculated. Receiver operating characteristic curve (ROC) analyses were performed to determine the optimal visual grade, to calculate cut-off values of quantitative indices, and to compare visual and quantitative diagnostic performances.. When over grade 3 of visual grade was used as cut-off value in the defection of primary breast cancer, the sensitivity and specificity were 75.5 and 80.8%, respectively. The positive and negative predictive values were 88.1 and 63.6%, respectively. The area under curve was 0.824 (95% CI, 0.719-0.902) and standard error (S.E.) was 0.047. The optimal L/N ratios were 3.13 for early and 2.56 for delayed image. When early L/N 3.13 was used as cut-off point, the sensitivity and specificity of TF-SMM were 61.2 and 96.2%, respectively. The positive and negative predictive values were 96.8 and 56.8%, respectively. The AUC was 0.809 (95% CI, 0.702-0.890) and S.E. was 0.049. When delayed L/N 2.56 was used as cut-off value, the sensitivity and specificity were 46.9 and 96.2%, respectively. The positive and negative predictive values were 95.8 and 49%, respectively. The AUC was 0.741 (95% CI, 0.627-0.835) and S.E. was 0.057. No statistical differences between visual assessment and quantitative analysis of early image (difference between area, 0.015; S.E., 0.044; 95% CI, -0.072 to 0.102; p = 0.736) and delayed image (difference between area, 0.083; S.E., 0.054; 95% CI, -0.023 to 0.060; p = 0.189) was noted. However, early L/N was superior to delayed L/N ratio for the detection of breast cancer (difference between area, 0.068; S.E., 0.033; 95% CI, 0.004-0.132; p = 0.038).. In conclusion, TF-SMM showed a favorable diagnostic accuracy in differentiating benign from malignant breast lesions. The optimal visual interpretation grades for the detection of primary breast cancer of double phase TF-SMM were grade 4 and 5. The optimal quantitative indices for the detection of breast cancer were 3.12 for early L/N and 2.56 for delayed L/N. Visual and quantitative analyses showed similar results. However, early L/N was superior to delayed one for the detection of breast cancer. Therefore, the delayed image should not be routinely performed for the purpose of primary breast cancer detection. These findings deserve further investigation on a larger number of patients to be performed to allow a better validation of the differentiation malignant from benign breast lesions using double phase TF-SMM.

Topics: Breast Neoplasms; Female; Gamma Cameras; Humans; Image Processing, Computer-Assisted; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; ROC Curve; Sensitivity and Specificity

The aim of this study was to evaluate the accuracy of breast cancer seeking agent Tc-99m-Tetrofosmin in the detection of breast malignancy and axillary lymph node metastases.. Twenty-eight female patients (mean age 52.4) with 30 breast lesions suspected of malignancy were enrolled in the study. All the patients underwent clinical investigation, Tc-99m Tetrofosmin scintimammography (SMM), mammography (MM) and biopsy/surgery for final histopathologic diagnosis. Patients were injected intravenously with 555 MBq of Tc-99m Tetrofosmin, cubitally, in the contralateral arm to the side of suspicious lesion. Seven minute static scans or at least 2.0 million counts were obtained using single head gamma camera (Orbiter 75, Siemens). Planar images were acquired in left and right prone lateral view as well as in the supine position for an anterior view of chest and axillary region.. SMM scans of 30 breast lesions were compared to the definitive histopathology findings (HP) using decision matrix. In the group of 23 patients with positive SMM scans 19 had breast malignancy: 15 infiltrating ductal cancer, three patients with one infiltrating lobular, one papillary, one colloidal cancer and one patient with cystosarcoma phyllodes-malignant type. SMM detected primary breast malignancy with 95% sensitivity, 60% specificity and 83% accuracy. Axillary dissection was performed in 19/20 with malignant disease. The number of lymph nodes extracted and HP evaluated varied from 4 to 23 per patient. Metastatic involvement was confirmed by HP in 9 out of 20 patients. SMM detected axillary metastases with 55% sensitivity and 80% accuracy.. Our results showed that SMM might be useful as a complementary test to improve the sensitivity and specificity of conventional imaging modalities, although SMM in the staging of breast carcinoma was less reliable. Further studies to evaluate the role of SMM in metastatic node involvement are necessary.

Topics: Aged; Biopsy; Breast Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals

(99m)Tc-sestamibi (MIBI) and (99m)Tc-tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging.. Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session.. MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62+/-0.15 vs. 0.55+/-0.05, P<.05) for TF and 1.9-fold (1.21+/-0.04 vs. 0.64+/-0.05, P<.05) for MIBI but did not affect MCF7/WT.. The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

Topics: Adenocarcinoma; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blotting, Western; Breast Neoplasms; Cyclosporins; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Metabolic Clearance Rate; Mice; Mice, SCID; Organ Specificity; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Transplantation, Heterologous; Tumor Cells, Cultured

Breast carcinoma is the most common neoplasm found among women in the Western world. Mammography (MM) is the most widely used diagnostic imaging method for screening and diagnosing breast cancer. However, despite technical improvements in recent years, MM has known diagnostic limits; consequently not all breast carcinomas are identified on mammograms, especially if the breast is dense, there is a breast prosthesis or the patient has previously undergone radiation, surgery or biopsy. In addition, the mammographic images of benign and malignant lesions can be similar. Therefore, abnormalities detected on MM frequently result in negative biopsies. Scintimammography (SM) is the functional imaging study of the breast using primarily the radiopharmaceuticals (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. The main advantage of SM is that its functional basis makes this technique a useful complement to MM. SM resolves some of the main limitations of MM as it is not affected by changes in breast morphology. Several single-site and multi-centre studies have demonstrated that SM has an improved specificity compared with MM, because it is better able to distinguish malignant from benign breast lesions. Interestingly, except in smaller lesions, a higher sensitivity has been recorded for SM than for MM in most of these studies as well. Adjunctive use of SM when MM is equivocal can reduce the number of unnecessary breast biopsies and identify previously unexpected sites of breast cancer. SM appears unaffected by the anatomical changes seen following chemotherapy and radiotherapy, and so this technique can be particularly useful in monitoring the treatment of breast cancer patients, especially when breast-conserving treatment is given. The main limitation to SM has been the sub-optimal resolution of the standard Anger gamma camera, which makes it difficult to detect lesions of less than 10 mm; however, the development of high-resolution breast-dedicated gamma cameras may offer improvements in this respect. This review will look at the evidence for SM and show how it can become part of the clinical care algorithm in breast cancer.

Topics: Breast Neoplasms; Clinical Trials as Topic; Humans; Lymphatic Metastasis; Organophosphorus Compounds; Organotechnetium Compounds; Practice Patterns, Physicians'; Prognosis; Radiopharmaceuticals; Risk Assessment; Risk Factors; Technetium Tc 99m Sestamibi; Technology Assessment, Biomedical; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

99mTc tetrofosmin scintimammography has been shown to be an accurate diagnostic test in patients with a symptomatic breast lesion and for whom a non-diagnostic mammogram has been obtained. Since a physical examination and conventional imaging modalities have their limitations in the detection of recurrent breast cancer, and survival is related to the extent of recurrent disease, complementary imaging modalities are warranted.. To evaluate the role of 99mTc tetrofosmin scintimammography in detecting the recurrence of loco-regional breast cancer.. Fifty-four patients underwent 55 scintimammography studies because either there were clinical indications of breast metastases, or there was a recurrence of metastases in the chest wall, and/or an evaluation of axillary, parasternal, supraclavicular and/or infraclavicular lymph node metastases was required. Planar breast imaging was performed 10 min after intravenous injection of 700 MBq 99mTc tetrofosmin.. 99mTc tetrofosmin scintimammography was diagnostic in 50 of the 55 studies. An unknown lung metastasis was detected in one patient, and an unknown bone metastasis of the sternum was detected in another. Tumour involvement remained undetected in one neck node metastasis. Three patients had false positive scintimammography results, with 99mTc tetrofosmin uptake in an axillary, infraclavicular and parasternal lymph node, respectively. A fourth patient showed 99mTc tetrofosmin uptake in the scar, which appeared to be an inflammatory lesion, proven by a histopathological biopsy and 1 year clinical follow-up.. 99mTc tetrofosmin scintimammography accurately detected 100% of the local recurrences independently of the extent of the preceding surgical intervention. The sensitivity and specificity of the technique for the detection of regional recurrent disease were 93% and 90%, respectively. These results are substantially higher than those of other imaging modalities.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Breast Neoplasms; False Positive Reactions; Female; Head and Neck Neoplasms; Humans; Injections, Intravenous; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mastectomy; Middle Aged; Neoplasm Recurrence, Local; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies; Thoracic Wall

Previous reports have demonstrated the feasibility of scintigraphic assessment of the multi-drug resistance (MDR) of tumours caused by ATP binding cassette (ABC) transporters by using Tc cationic tracers such as Tc tetrofosmin (TF). Furthermore, the potential of these tracers for evaluating the effects of reversal agents for MDR has been documented. However, most reversal agents simultaneously affect cationic ion transporters related to tracer accumulation in tumours.. The uptake of Tc-TF was examined in the MCF7/WT cell line, a wild-type breast cancer cell line that does not exhibit MDR, and its subclonal etoposide resistant cell line MCF7/VP, which expresses high levels of MRP1, one of the multi-drug resistance associated proteins (MRPs), in the presence of increasing concentrations of verapamil, a classical MDR modulator. In the absence of verapamil, MCF7/VP cells showed significantly lower Tc-TF uptake than did MCF7/WT cells, indicating that Tc-TF is a substrate for MRP1. The presence of verapamil enhanced the uptake of Tc-TF in MCF7/VP cells. On the other hand, verapamil also increased tracer uptake in MCF7/WT cells, which was readily appreciated when the uptake values were corrected by viable cell numbers: an approximately 100% increase of Tc-TF uptake was observed in comparison with that in the absence of verapamil in viable MCF7/WT cells whereas a 100-200% increase occurred in viable MCF7/VP cells. In addition, verapamil prolonged the retention of radioactivity in both MCF7/WT cells and MCF7/VP cells.. These results suggest that cellular functions other than MRP1 function, probably cationic ion transporters, are simultaneously and significantly involved in the verapamil induced changes of cellular uptake of Tc-TF. Tc-TF scintigraphy may overestimate the reversal effects of modulators on chemoresistance caused by MRP1 when the modulators simultaneously affect ion transporters.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Humans; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Treatment Outcome; Verapamil

Topics: Aged; Breast Neoplasms; Coronary Artery Disease; Female; Heart; Humans; Incidental Findings; Mastectomy, Modified Radical; Neoplasm Recurrence, Local; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals

Dedicated mammotomography with pinhole incomplete circular orbit (PICO) SPECT imaging of an uncompressed pendant breast was evaluated with small, very-high-stopping-power pinhole apertures. Comparisons were made with planar pinhole scintimammography. Enhanced 3-dimensional imaging performance with very-high-stopping-power apertures is thought to ultimately yield improved sensitivities for lesion detection and identification in breast disease.. Pinhole collimators made of high-density and high atomic number (184)W or depleted (238)U, with aperture diameters from 1 to 4 mm, were used to image 0.6- and 1.0-cm-diameter spherical lesions in a pendulous, uncompressed breast phantom in planar and PICO-SPECT modes. The breast was centered on the horizontal axis of rotation of an incomplete circular orbit. Lesion, breast and body, and myocardial activities (L:B:M) were included in the phantoms to simulate clinical imaging conditions with (99m)Tc (140 keV). Lesion contrasts and signal-to-noise ratios (SNRs) for all apertures were determined for near clinical acquisition times for L:B:M ratios of 12:1:20 and 7:1:25. A set of minidisks inserted in the breast phantom was scanned to determine sampling limitations at depth from the nipple. In an initial study, a patient with biopsy-confirmed breast carcinoma was injected with 960 MBq (99m)Tc-tetrofosmin and scanned 2 h later with planar pinhole and PICO-SPECT techniques.. Overall, for PICO-SPECT imaging there were small differences in measured counting rate sensitivity (4.9%) and lesion contrast (8.8%) with larger SNR differences (20.8%) between tungsten and depleted uranium pinhole materials at this energy and these lesion sizes. Backgrounds from simulated myocardial uptake had minor contributions in all reconstructed image volumes because of the rapid sensitivity fall-off for pinhole apertures. An optimal aperture diameter between 2 and 3 mm was determined from peak SNR, indicating that these aperture sizes may have the best performance for lesions as small as 0.6 cm in diameter with activity concentration ratios of (99m)Tc similar to those currently seen in patients. Both lesions were visualized with PICO-SPECT better than with planar pinhole imaging, with respective contrast improvements >20 times the values obtained from planar imaging for the same pinholes. In the patient study, higher contrast (>6) visualization of the active tumor periphery was obtained with PICO-SPECT than with planar imaging.. These results indicate that the enhanced spatial resolution of smaller apertures outweighs the loss in sensitivity in small lesion identification with PICO-SPECT. Although the imaging differences between investigated aperture types are small and some limitations to this imaging approach exist, dedicated PICO-SPECT of the breast appears to be an improved technique compared with conventional planar pinhole scintimammography. This technique provides enhanced contrast and SNR for imaging small lesions with the high-resolution pinhole apertures along with 3-dimensional localization of the lesions.

Topics: Breast; Breast Neoplasms; Female; Humans; Image Enhancement; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Phantoms, Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Topics: Breast Neoplasms; Coronary Disease; Echocardiography; Electrocardiography; Female; Humans; Image Interpretation, Computer-Assisted; Middle Aged; Neoplasm Staging; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Radiotherapy

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.

Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Hypoxia; Cell Line, Tumor; Humans; Metabolic Clearance Rate; Multidrug Resistance-Associated Proteins; Organophosphorus Compounds; Organotechnetium Compounds; Oxygen; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi

The purpose of this study was a retrospective survey of 40 patients with infiltrating ductal breast carcinoma to evaluate the relationships between the degree of accumulation of technetium-99m tetrofosmin (Tc-TF), multidrug resistance-related protein (MRP) expression and P-glycoprotein (Pgp) expression in breast cancer tissue. Immunohistochemical analysis (IHA) was performed on pathological specimens of the 40 breast cancers to determine Pgp and MRP expression. The results of IHA, were used as the basis for dividing the 40 breast cancers into four groups: A, 10 tumors with positive MRP and Pgp expressions; B, 10 tumors with positive MRP but negative Pgp expression; C, 10 tumors with negative MRP but positive Pgp expression; and D, 10 tumors with negative MRP and Pgp expression. All 40 patients had undergone Tc-TF mammoscintigraphy to calculate breast cancer uptake of Tc-TF to background uptake (T/B) ratios before IHA and surgery/biopsy. Of the four groups, group A had the lowest T/B ratios (1.15+/-0.10) and group D, the highest (2.19+/-0.15) (P<0.05). The T/B ratios in groups B (1.36+/-0.27) and C (1.37+/-0.26) were intermediate between those of groups A and D. In addition, the T/B ratios were statistically significantly lower in group A than in group B or C, and statistically significantly higher in groups D than in groups B or C (P<0.05). However, no significant difference in T/B ratio was found between groups B and C (P>0.05). Our results indicate that Tc-TF mammoscintigraphy is helpful for in vivo determination of Pgp and MRP expression in breast cancers.

Topics: Adult; Aged; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Carcinoma, Ductal, Breast; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Random Allocation; Retrospective Studies

Topics: Breast; Breast Neoplasms; Europe; Humans; Nuclear Medicine; Organophosphorus Compounds; Organotechnetium Compounds; Patient Care Management; Practice Guidelines as Topic; Practice Patterns, Physicians'; Radiopharmaceuticals; Societies, Medical; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed

To evaluate radiation-induced defects in myocardial perfusion imaging in early breast cancer patients treated with modern technique radiotherapy.. Twenty-four patients with left-breast tumours and 12 control patients with right-breast tumours, relapse-free since treatment for primary disease, who had undergone radiotherapy at least 5 years previously and with no history of ischaemic heart disease prior to radiotherapy underwent study. In left-breast patients, at least 1 cm of heart was required to have been in the treatment field. Patients underwent cardiac assessment and single photon emission computerized tomography myocardial perfusion imaging.. Myocardial perfusion tracer uptake was abnormal in 17 (70.8%) left-breast and two (16.7%) right-breast patients (P = 0.002). Of the 17 abnormal scans in left-breast patients, abnormalities were confined to the cardiac apex in 16 patients, and perfusion defects were reversible (n = 7), fixed (n = 7) or mixed (n = 3). Reversible perfusion defects that were not confined to the cardiac apex were observed in two right-breast patients. Left ventricular ejection fraction was normal in all 33 patients in whom it was measured, and no myocardial perfusion abnormalities were judged to require treatment or follow-up.. In this selected study population modern technique radiotherapy to the left breast was associated with a significantly greater number of myocardial perfusion abnormalities than radiotherapy to the right breast. These abnormalities were both reversible and irreversible, suggesting that radiotherapy can lead to both myocardial damage and to epicardial coronary disease. With a minimum of 5 years follow-up since treatment, no abnormalities were considered to be clinically significant.

Topics: Aged; Breast Neoplasms; Coronary Circulation; Female; Follow-Up Studies; Heart; Humans; Middle Aged; Myocardial Ischemia; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Radiotherapy; Risk Factors; Tomography, Emission-Computed, Single-Photon

The aim of this study was to evaluate the usefulness of supine 99mTc-tetrofosmin SPECT in the detection of small size breast carcinomas (BC), for which planar scintimammography has showed a low sensitivity. We studied 93 patients with breast lesions

Topics: Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Male; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

The aim of our study was to compare the usefulness of technetium-99m tetrofosmin (Tc-TF) mammoscintigraphy and ultrasonography for detecting breast cancer in mammographically dense breasts. This study included 32 female Taiwanese patients with indeterminate mammographic probability of malignancy due to mammographically dense breasts. Both Tc-TF mammoscintigraphy and ultrasonography were performed on each patient. Then, all of the 32 breast masses underwent biopsies or operations to obtain final pathological diagnoses. Based on the final pathological diagnoses, 24 women had breast cancer and eight had benign breast tumors among the 32 patients. Twenty cancers and one benign tumor had positive Tc-TF mammoscintigraphic findings. The sensitivity, specificity, and accuracy were 83, 88, and 84%, respectively. Twenty-two cancers and five benign tumors had positive ultrasonographic findings. The sensitivity, specificity, and accuracy were 92, 38, and 78%, respectively. To detect breast cancer in patients with nondiagnostic mammograms because of mammographically dense breasts, ultrasonography with its higher sensitivity is more suitable for screening breast masses. However, due to its higher specificity, Tc-TF mammoscintigraphy is useful to confirm the ultrasonographic findings.

Topics: Adenocarcinoma; Adult; Aged; Breast; Breast Neoplasms; Diagnosis, Differential; False Positive Reactions; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography, Mammary

We have investigated the usefulness of dual-isotope single photon emission computed tomography (SPECT) for predicting the response to chemotherapy in patients with breast cancer. Twenty-five patients with breast cancer were analyzed by SPECT using both 99m-technetium-tetrofosmin (99mTc-TF) and 201-thallium-chloride (201Tl). The relationship between response to chemotherapy and retention of each tracer was analyzed. 99mTc-TF retention was significantly higher in responders (42.0+/-37.9) than in non-responders (-11.3+/-34.6) (p=0.003). Ten of 13 patients (76.9%) with high 99mTc-TF retention (>15%) showed good response to chemotherapy, whereas 11 of 12 patients (91.7%) with low 99mTc-TF retention (<15%) did not respond to the therapy. The overall predictability to the response to chemotherapy was 84.0%. 201Tl retention (responders, 47.5+/-60.2% vs. non-responders, 55.8+/-45.0%; p=0.443) was not useful in therapeutic prediction, but was required to identify the lesion on the SPECT image. This is the first report to find that dual-isotope SPECT using 99mTc-TF and 201Tl is useful in predicting the response to chemotherapy in patients with breast cancer. Low 99mTc-TF retention is a strong predictor of therapeutic resistance, and high 99mTc-TF retention suggests a favorable response to chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Prognosis; Radiopharmaceuticals; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

The most important prognostic factor in breast (B) cancer (C) is axillary (A) lymph (L) node (N) status, and virtually all patients with BC undergo ALN dissection to assess N involvement. The aim of this study was to evaluate the accuracy of planar and tomographic Tc-99m tetrofosmin scintigraphy in the detection of ALN involvement in BC. A group of 85 female patients (age range: 31-82 years) with 87 BCs were studied before surgery. Three planar images, right and left prone lateral and supine anterior thoracic views, and 360 degrees supine thoracic single photon emission tomography (SPET) were acquired after Tc-99m tetrofosmin injection (740 MBq i.v.). ALN status was evaluated by histological exam after A dissection: metastatic ALN involvement was proved in 31 out of 87 cases. Sensitivity was 87.1% (27/31) for SPET and 61.3% (19/31) for planar images (p<0.01); specificity was 92.9% (52/56) and 94.6% (53/56), respectively, with a global accuracy of 90.8% (79/87) for SPET and 82.8% (72/87) for planar imaging (p<0.05). Sensitivity rose from 75% in non-palpable Ns to 94.7% in palpable ones for SPET, and from 41.7 to 73.7% for planar scans. SPET was positive in 17/18 (94.4%) patients with >3 metastatic Ns and in 10/13 (76.9%) with < or = 3 involved Ns, whereas planar images were positive in 14/18 (77.8%) and in 5/13 (38.5%) cases, respectively. In conclusion, our findings indicate that Tc-99m tetrofosmin scintigraphy is useful in the presurgical detection of ALN metastases in BC, with SPET more accurate than conventional planar images, thus suggesting its more frequent use in scintimammography; moreover, the total number of histologically involved Ns can affect the scintigraphic results.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Metastasis; Organophosphorus Compounds; Organotechnetium Compounds; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Adjuvant and neoadjuvant chemotherapy is being used increasingly in the treatment of breast cancer patients. However, drug resistance plays an important role in the failure of chemotherapy in breast cancer. The aim of this study was to compare technetium-99m tetrofosmin (Tc-TETRO) mammoscintigraphic findings with the expression of drug resistance proteins (p-glycoprotein [Pgp], Ki-67 and mutant p53) in human breast cancer tissues. Thirty patients diagnosed with infiltrating ductal breast cancer underwent Tc-TETRO mammoscintigraphy before surgery or biopsy. Protein expression was investigated by immunohistochemical analyses on multiple nonconsecutive sections from surgery or biopsy specimens. Tumor to background (T/B) ratios calculated by Tc-TETRO mammoscintigraphic findings were correlated with protein expression determined by immunohistochemical analyses. The Tc-TETRO T/B ratios were significantly lower for tumors in 12 patients with positive Pgp expression than for those in 18 patients with negative expression (1.19 +/- 0.13 and 1.94 +/- 0.33, p value < 0.01). However, differences in Tc-TETRO T/B ratios between the patients with positive and negative Ki-67 or mutant p53 expression were not found in this study. Our data confirmed that Tc-TETRO mammoscintigraphic findings are useful for determination of the presence of Pgp expression in breast cancer patients, but no significant relations between Tc-TETRO mammoscintigraphic findings and Ki67 or mutant p53 were found.

Topics: Adult; Aged; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Mammography; Middle Aged; Neoplasm Staging; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Estrogen; Receptors, Progesterone; Tumor Suppressor Protein p53

The purpose of this study was to assess the usefulness of techentium-99m tetrofosmin (Tc-TF) scintimammography to detect breast cancer in 32 female Taiwanese patients with indeterminate mammograpic probability of malignancy because of mammographyically dense breasts. All breast masses were removed and final histopathological diagnoses were obtained in all cases. The results showed that Tc-TF scintimammography findings were true-positive in 20 cases, false-positive in 1 case, true-negative in seven cases, and false-negative in four cases. The diagnostic sensitivity, specificity, and accuracy were 83, 88, and 84%, respectively, for detecting breast cancer in mammographically dense breasts. In conclusion, Tc-TF scintimammography is a useful tool for detecting breast cancer in patients with indeterminate mammograms because of mammographically dense breasts.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; False Negative Reactions; Female; Fibroadenoma; Humans; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Papilloma, Intraductal; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity

Topics: Breast Neoplasms; Female; Humans; Mammography; Mass Screening; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Breast Neoplasms; Clinical Trials as Topic; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Neoplasm Proteins; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Patient Selection; Radionuclide Imaging; Radiopharmaceuticals; Substrate Specificity; Technetium Tc 99m Sestamibi

99Tcm-methoxyisobutylisonitrile (99Tcm-MIBI) and 99Tcm-tetrofosmin are cationic tracers recognized by the efflux pump P-glycoprotein (Pgp). Verapamil has been shown to be a competitive inhibitor of Pgp, and was one of the first multidrug-resistant reversing agents identified. The aim of this preclinical in vitro study was to evaluate the effects of verapamil on the accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in the human breast cancer cell lines MCF-7 and SK-BR-3 and in the human soft tissue sarcoma cell lines SW 982 and SW 1353, in comparison with respective control cells, i.e. without preincubation with verapamil. After preincubation with 10 or 100 microM of verapamil for 15 or 30 min, the 99Tcm-MIBI and 99Tcm-tetrofosmin accumulation in cells was assessed at 10, 30 and 60 min after incubation with these tracers. Addition of verapamil caused a decline in the accumulation of the two tracers at all incubation times, as compared with control cells. These effects of verapamil were neither dose- nor preincubation time-dependent in most cells. Our data indicate that verapamil is not a promising agent for increasing the sensitivity of scintigraphy with 99Tcm-MIBI or 99Tcm-tetrofosmin, or for evaluating Pgp tumour status in these types of tumours.

Topics: Adenocarcinoma; Breast Neoplasms; Calcium Channel Blockers; Cell Line; Cell Survival; Female; Humans; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Sarcoma; Soft Tissue Neoplasms; Technetium Tc 99m Sestamibi; Tumor Cells, Cultured; Verapamil

The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of 99mTc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of 99mTc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 microg/ml of tea polyphenol respectively. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 microM of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Drug Interactions; Drug Resistance, Multiple; Flavonoids; Organophosphorus Compounds; Organotechnetium Compounds; Phenols; Plant Extracts; Polymers; Polyphenols; Quinidine; Tea; Tumor Cells, Cultured

The aim of this study was to evaluate the usefulness of (99m)Tc-tetrofosmin single-photon emission tomography (SPET) in the detection of both primary breast cancer and axillary lymph node metastasis. We studied 192 consecutive patients in whom primary breast cancer was suspected on the basis of mammography and/or physical examination. After intravenous injection of 740 MBq (99m)Tc-tetrofosmin, both planar and SPET scintimammography was performed in all patients using a rectangular dual-head gamma camera equipped with low-energy, high-resolution, parallel-hole collimators. In 175 patients with breast cancer at histology, the per-lesion overall sensitivity of SPET and planar imaging for the detection of breast cancer was 95.8% and 75.9% (P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 96.5% and 79.5% in palpable (P<0.0005) and 90% and 45% in non-palpable lesions (P<0.01). With regard to lesion size, the sensitivity of SPET and planar imaging was, respectively, 90.5% and 45.2% in lesions < or =10 mm ( P<0.0005), 95.3% and 81.4% in lesions of 11-20 mm (P<0.005), 100% and 84.6% in lesions of 21-30 mm (P<0.05) and 100% and 95.8% in lesions >30 mm (P>0.05). In the remaining 17 patients with benign mammary lesions at histology, per-lesion overall specificity of SPET and planar imaging was 76.2% and 85.7% (P>0.05), respectively. Neither SPET nor planar imaging showed false-positive results in non-palpable lesions or in those < or =10 mm. In 173 breast cancer patients submitted to axillary lymph node dissection (ALND), per-axilla overall sensitivity of SPET and planar imaging in the detection of axillary lymph node metastasis was 93% and 52.3% ( P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 100% and 82.6% in palpable nodes (P>0.05), 90.5% and 41.3% in non-palpable nodes (P<0.0005), 92.8% and 35.7% in the presence of < or =3 nodes ( P<0.0005) and 93.2% and 68.2% in the presence of >3 nodes (P<0.005). The specificity of SPET and planar imaging was 91% and 100% (P<0.05), respectively. (99m)Tc-tetrofosmin SPET appears to be a reliable method for the detection of both primary BC and axillary lymph node metastasis, and its diagnostic accuracy exceeds that of (99m)Tc-tetrofosmin planar scintimammography. The use of SPET is particularly important in the identification of small non-palpable primary carcinomas and metastatic axillae with < or =3 non-palpable lymph nodes. More extensive use of SPE

Topics: Axilla; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma, Ductal, Breast; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

We compared 99mTc-Tetrofosmin P-SPECT with radioguided SN biopsy in 101 T1/T2 BC pts to predict axillary lymph node status. The day before surgery all pts underwent lymphoscintigraphy (LS) to mark the SN, following subdermal injection of 99mTc-colloidal sulphur surrounding the breast lesion. LS was combined with pre and intraoperative gamma probe. Previously, all pts had also undergone P-SPECT. ALND was performed in all cases. The SN(s) was detected in 97/101 cases (96%) by LS and gamma probe; in the 4 missed cases P-SPECT predicted lymph node status. In the 97 comparable cases, radioguided SN biopsy showed a slightly higher accuracy than P-SPECT (94.8% vs 93.8%), but a higher false-negative rate (14.3% vs 8.6%); P-SPECT had a higher NPV (95.2% vs 92.5%). The two procedures when combined achieved 100% accuracy. Radioguided SN biopsy alone had 100% accuracy only in pts with BC < 15 mm. P-SPECT had 3 false negative cases, 2 of which were micrometastatic SNs, and 3 false positives. P-SPECT identified 81.2% of cases with a single node, determined the exact number of nodes in 82.6% of cases with 1 to 3 node and correctly classified 93.7% of pts as having < or = 3 or > 3 metastatic nodes. Radioguided SN biopsy seems indicated in selected, early stage, small BC pts, while P-SPECT shows a high sensitivity independent of primary tumor size, giving additional important preoperative prognostic information. The two procedures combined provided a better axillary lymph node status prediction in T1/T2 carcinomas, and could thus improve ALND pt selection.

Topics: Adult; Aged; Axilla; Biopsy, Needle; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Radiopharmaceuticals; Sentinel Lymph Node Biopsy; Tomography, Emission-Computed, Single-Photon

The number of metastatic axillary nodes represents one of the most important prognostic factors in preoperative breast cancer patients. 99mTc-Tetrofosmin high resolution Pinhole (P)-SPECT was employed in 112 patients, 100 with breast cancer and 12 with benign mammary lesions, to ascertain axillary lymph node involvement. Axillary P-SPECT images were acquired utilizing specific software connected to a circular high resolution, single-head gamma camera equipped with a pinhole collimator with aperture size of 4.45 mm, rotating 180 degrees around the involved axilla. At the same time, patients also underwent conventional SPECT and planar acquisitions. Per-patient sensitivity and specificity were 100% and 93.6% for P-SPECT, 96.2% and 93.6% for SPECT and 56.6% and 100% for planar imaging, respectively. Moreover, P-SPECT detected more than 51% of lesions ascertained by histology, whereas SPECT and planar detected 32.6% and 20.3%, respectively. Only P-SPECT succeeded in identifying the exact number of metastatic axillary lesions in patients with multiple nodes; this procedure was able to correctly differentiate 88.67% of patients with 3 or less nodes from those with more than 3, thus giving important prognostic information. These data suggest 99mTc-Tetrofosmin P-SPECT is a reliable imaging method both for staging and prognostic purposes in breast cancer, and its routine use is recommended.

Topics: Adult; Aged; Breast Neoplasms; Breast Neoplasms, Male; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

The kinetics and cellular uptake of 99mTc-2-hexakis 2-methoxyiso-butyl-isonitrile (MIBI) and 99mTc-1 ,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) into malignant versus nonmalignant human breast cell lines were investigated and compared.. At specific intervals after incubation at 37 degrees C and 22 degrees C with 99mTc-MIBI or 99mTc-tetrofosmin, the uptake characteristics of radiotracers into human adenocarcinoma breast cell lines MCF-7 and SK-BR-3 and human breast, nontumor cell line HBL-100 were assessed.. The uptake of 99mTc-MIBI and 99mTc-tetrofosmin was lower at an incubation temperature of 22 degrees C than that at 37 degrees C in the 3 cell lines. In MCF-7 and in SK-BR-3 cells the uptake of 99mTc-MIBI was significantly higher than the uptake of 99mTc-tetrofosmin. The uptake of 99mTc-MIBI was significantly higher into MCF-7 and SK-BR-3 cells than that into HBL-100 cells. In comparison with HBL-100 cells, uptake of 99mTc-tetrofosmin into SK-BR-3 cells was significantly higher, whereas uptake into MCF-7 cells was similar.. In vitro data suggest that 99mTc-MIBI may be a better tracer than 99mTc-tetrofosmin for discrimination between malignant and nonmalignant breast disease.

Topics: Adenocarcinoma; Biological Transport; Breast; Breast Neoplasms; Cell Line; Female; Humans; Kinetics; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Tumor Cells, Cultured

To assess the value of 99m-Tc-tetrofosmin (tetrofosmin) scintigraphy in patients with palpable and nonpalpable breast lesions.. Prospective, blinded trial. One hundred and fifty-nine consecutive patients with 163 breast lesions detected by clinical examination and mammography were included. Tetrofosmin scintigraphy of the breast was performed additionally to the regular diagnostic procedure. Using histologic assessment as the golden standard, sensitivity, specificity, positive and negative predictive value for tetrofosmin scintigraphy of the breast were assessed.. Overall sensitivity and specificity were 82% and 84%. The sensitivity for palpable tumors (65%) was 93% compared to 62% for non-palpable breast lesions. Malignant lesions were nearly twice as big as benign lesions (31.5 mm +/- 2.4 vs. 16.9 mm +/- 2.4). Specificity, positive and negative predictive value (84%, 89%, and 66%) did not differ significantly in palpable versus non-palpable tumors. Of malignant tumors 18% were found false negative by tetrofosmin scintigraphy.. The results suggest that tetrofosmin scintigraphy is a valuable tool for the evaluation of palpable breast cancer. In patients with non-palpable tumors, tetrofosmin scintigraphy may not add to the work-up of patients with breast cancer due to a low sensitivity rate.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Palpation; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Sensitivity and Specificity; Single-Blind Method

Topics: Breast; Breast Neoplasms; Female; Humans; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity

Recent reports consider 99mTc-tetrofosmin scintigraphy to be a powerful new diagnostic tool for discriminating malignant from benign breast disease. We report on a woman suffering from histologically confirmed axillary metastases of a primary unknown, occult carcinoma, whose origin was suspected within the breast. All the diagnostic procedures performed to discover any lesion failed or were inconclusive. The primary cancer was clearly visualized, however, in the right breast by means of 99mTc-tetrofosmin scintigraphy. Conclusion. We suggest that 99mTc-tetrofosmin scintigraphy is a powerful method to detect breast cancer, especially when other diagnostic imaging procedures are inconclusive.

Topics: Axilla; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasms, Unknown Primary; Organophosphorus Compounds; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon

To assess the contribution of 99mTechnetium tetrofosmin (99mTc-TF) scintimammography for staging of breast lesions in patients with a suspicious or non-diagnostic mammogram to reduce unnecessary surgical procedures in future.. Fifty patients with suspicious physical examinations and/or mammography underwent 99mTc-TF breast imaging.. Scintimammography with 99mTc-TF was positive in 37 patients (36 true positive, one false positive) and negative in 13 patients (12 true negative, one false negative). The detection of a malignant tumour by 99mTc-TF was independent of the density of the breast tissue. In 33 patients with a malignant breast tumour 99mTc-TF was diagnostic with respect to axillary status, but in four out of 19 patients with a histologically positive axillary lymph node status, tumour involvement remained undetected by scintigraphy. Moreover, in four patients, scintimammography revealed an additional discrete area of increased 99mTc-TF uptake, which proved to be second primary breast cancers.. 99mTc-TF scintimammography appears to be an accurate diagnostic test in patients with a symptomatic breast lesion and a non-diagnostic mammogram, also in those patients with dense breast tissue. This procedure may also have potential for the detection of second primary breast cancers in an early stage.

Topics: Adult; Aged; Breast Neoplasms; Female; Humans; Lymphatic Metastasis; Mammography; Middle Aged; Neoplasms, Second Primary; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals

To assess the role of Technetium-99m (99mTc) tetrofosmin scintimammography in the detection of breast cancer and involvement of axillary nodes.. Open study.. General hospital, Turkey.. 128 women who presented with masses in the breast.. Scintimammography, standard mammography, and either excision or fine-needle aspiration biopsy to confirm the diagnosis.. Sensitivity, specificity, and positive and negative predictive value of scintimammography compared with mammography.. Sensitivity, specificity, and positive and negative predictive value (%) of 99mTc scintimammography were 95, 96, 97 and 92, respectively. The corresponding figures for standard mammography were 87, 26, 68 and 52. Scintimammography changed the 34 false positive mammograms into true negatives, at the expense of four false negatives. The sensitivity of scintimammography in detecting axillary lymph node metastases was 72% and specificity 100%.. Scintimammography with 99mTc tetrofosmin seems to be of value in the detection of breast malignancy and axillary metastases. It may help to avoid unnecessary operations in patients whose mammograms do not give a definite diagnosis.

Topics: Adult; Aged; Axilla; Biopsy, Needle; Breast; Breast Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Mammography; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity

The aim of this study was to compare uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-Q12 in vitro and biodistribution in vivo in rats. In vitro, uptake decreased in the order MIBI-->tetrofosmin-->Q12. Uptake of MIBI and tetrofosmin, but not of Q12, in cultured tumor cells was dependent on the plasma membrane and mitochondrial potential. In vivo, heart uptake of all three compounds was high and stable. Tumor uptake decreased in the order MIBI-->Q12-->tetrofosmin and the tumor/blood ratio in the order MIBI-->tetrofosmin-->Q12.

Topics: Animals; Biological Transport; Breast Neoplasms; Cell Membrane; Female; Furans; Humans; Kinetics; Male; Mitochondria; Myocardium; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Rats; Rats, Wistar; Technetium Tc 99m Sestamibi; Tissue Distribution; Tumor Cells, Cultured

Topics: Antineoplastic Agents; Breast Neoplasms; Humans; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Thyroid Gland; Tomography, Emission-Computed, Single-Photon

99mTc-tetrofosmin myocardial imaging was performed in a 62-year-old woman who had undergone standard radical mastectomy for right breast cancer 6 years ago. Although the result was negative for the ischemic heart disease, it showed abnormal accumulation corresponding to the bone metastases in the spine. We believe that 99mTc-tetrofosmin imaging is helpful in detecting bone metastases from breast cancer.

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Mastectomy, Radical; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Spinal Neoplasms; Tissue Distribution; Tomography, X-Ray Computed

201Tl and 99Tcm-MIBI have been used to evaluate palpable breast masses. The aim of this study was to evaluate the potential of 99Tcm-tetrofosmin as a new tumour localizing agent in patients with palpable breast masses. Nineteen palpable breast masses were evaluated in 18 patients. Each patient received 740 MBq 99Tcm-tetrofosmin intravenously. Ten minutes after the injection, planar breast images in the anterior, right lateral and left lateral views were obtained with the patient in the supine position. Mammography and ultrasonography were performed in all patients. Biopsy or mastectomy with axillary dissection was performed in all patients. Thirteen of 14 primary breast tumours were detected (9 invasive ductal carcinomas, 3 invasive lobular carcinomas, 1 papillary carcinoma). One patient with mucinous carcinoma did not demonstrate 99Tcm-tetrofosmin accumulation. Four of five patients with histopathologically proven benign lesions did not demonstrate 99Tcm-tetrofosmin accumulation (2 fibrocystic diseases, 2 fibroadenomas). 99Tcm-tetrofosmin accumulation was seen in a patient with chronic mastitis. The sensitivity and specificity of 99Tcm-tetrofosmin for malignant breast lesions was 92 and 80% respectively. Four of seven (57%) axillary lymph node metastases showed 99Tcm-tetrofosmin uptake. In conclusion, 99Tcm-tetrofosmin shows real promise for use in evaluating patients with palpable breast masses.

Topics: Adult; Aged; Breast; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Male; Mammography; Mastitis; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Physical Examination; Sensitivity and Specificity; Tomography, Emission-Computed

The aim of this exploratory study was to assess the potential of discriminating malignant from non-malignant lesions using 99Tcm-tetrofosmin scintimammography in the detection of palpable breast tumours. Nine patients with palpable masses were studied; seven had malignant lesions and two had non-malignant lesions. All diagnoses were established by fine-needle aspiration (FNA) biopsy cytology. Each patient received 925 MBq (25 mCi) 99Tcm-tetrosfosmin intravenously. Planar prone views were acquired in the right lateral, left lateral and anterior positions, and the axillary regions were included in the field of view. Scintimammography showed focally increased tracer uptake in seven patients with a positive FNA result. The two patients with a negative FNA result showed no increased uptake. We suggest that 99Tcm-tetrosfosmin shows promise as a radiopharmaceutical in the detection and discrimination of the nature of palpable breast tumours. Larger studies are required to confirm these findings.

Topics: Aged; Biopsy, Needle; Breast; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Palpation; Radionuclide Imaging; Radiopharmaceuticals

Breast cancer, the most common malignancy in women, still poses a challenge to diagnostic procedures and therapy. Despite low specificity routine mammography is the method of choice to screen women for breast cancer. In the last years other additional diagnostic procedures such as high frequency ultrasonography (US) and especially magnetic resonance imaging (MRI) have improved breast cancer diagnosis. However, all these imaging methods are lacking in specificity which makes biopsy or surgery necessary. The purpose of our study was to evaluate prospectively the sensitivity, specificity, PPV and NPV of scintimammography with a new cationic complex Tc-99m tetrofosmin in patients with suspicious mammographic lesions. One hundred and thirty seven patients in whom mammography and/or high resolution ultrasonography (10 MHz) revealed suspicious breast lesions were studied with Tc-99m tetrofosmin scintimammography. In 84 of them biopsy and/or surgery was performed for histological evaluation. After intravenous injection of 555 MBq Tc-99m tetrofosmin planar images in anterior and lateral projections (5 min.p.i.) and SPECT imaging including 3-D-reconstruction (20 min.p.i.) were performed. Scintimammography was evaluated as negative, equivocal (+), probably (+2) or definitely (+3) positive. Planar scintimammography with Tc-99m tetrofosmin was negative in 46 patients (43 true negative-f.n; 3 false negative-f.n.) and positive in 38 patients (27 true positive-t.p.; 11 false positive-t.p.). Using SPECT imaging Tc-99m scintimammography was negative in 43 cases (41 t.n.; 2f.n.) and positive in 41 cases (28 t.p.; 13 t.p). Sensitivity of Tc-99m tetrofosmin scintimammography in this prospective study was 90%, specificity 80%, PPV 71% and NPV 93% for planar imaging and 93%, 76%, 68% and 95% for SPECT, respectively. Scintimammographic results in patients with suspicious breast lesion show, that Tc-99m tetrofosmin accumulates in breast cancer as well as in some fibroadenoma with high cellularity. However, the high NPV of 93 and 95% respectively excludes breast cancer in suspicious mammographic lesions to a very high degree and therefore reduces the need of biopsy and/or surgery in most of these patients.

Topics: Adenocarcinoma; Adult; Aged; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Magnetic Resonance Imaging; Mammography; Middle Aged; Neoplasms, Multiple Primary; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Ultrasonography, Mammary

To compare technetium-99m tetrofosmin scintimammography with contrast material-enhanced magnetic resonance (MR) imaging in the characterization of palpable breast masses.. Forty-seven patients (mean age, 51 years) with a palpable breast mass were prospectively examined with scintimammography, MR imaging, and conventional mammography 2 weeks before fine-needle aspiration biopsy.. In three patients, MR imaging was aborted. Of the remaining 44 patients, 21 had biopsy-proved cancer and 23 had benign disease. The sensitivity of mammography was 81%; specificity, 82%; positive predictive value (PPV), 85%; and negative predictive value (NPV), 78%. The sensitivity of scintimammography was 95%; specificity, 91%; PPV, 91%; and NPV, 95%. The sensitivity of MR imaging was 90%; specificity, 91%; PPV, 90%; and NPV, 91%. In 11 patients with previous breast cancer, scintimammographic findings were positive in all four with tumor recurrence and negative in all seven with benign disease. Masses were correctly characterized with MR imaging in eight of these 11 patients.. Although both techniques accurately differentiate benign from malignant palpable breast masses, scintimammography is more accurate in the posttreatment breast. Because of lower cost, wider availability, and high patient acceptance, scintimammography may provide a valuable alternative to MR imaging for noninvasive characterization of palpable breast disease.

Topics: Adult; Aged; Biopsy, Needle; Breast; Breast Diseases; Breast Neoplasms; Contrast Media; Female; Gadolinium; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Mammography; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Organotechnetium Compounds; Palpation; Pentetic Acid; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Subtraction Technique

The uptake of 99mTc-tetrofosmin in enlarged lymph nodes, of the lung hilus, in the case of sarcoidosis Stage I (histopathologically confirmed by mediastinoscopic biopsy) is demonstrated. On a routine chest radiograph of a 78-yr-old woman, hilar lymphadenopathy was first detected. In the following mammography, disseminated micro calcifications were found in the left breast and a 99mTc-tetrofosmin study was performed for detection of breast cancer. Scintigraphy using 99mTc-tetrofosmin showed clear uptake in the hilar lymph nodes, but not in the left breast. The 99mTc-tetrofosmin uptake in the hilar lymph nodes was due to sarcoidosis confirmed by histology. Therefore, 99mTc-tetrofosmin scintigraphy may be useful in patients with suspected sarcoidosis, especially in Stage I.

Topics: Aged; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Lymph Nodes; Mediastinum; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Sarcoidosis; Tomography, Emission-Computed, Single-Photon

The potential of Tc-99m tetrofosmin for the imaging of breast carcinoma and axillary lymph node metastases was investigated and compared with that of Tc-99m MIBI. Thirty female patients with palpable breast masses underwent Tc-99m MIBI scintigraphy; 17 of those underwent Tc-99m tetrofosmin scintigraphy. The axillary and breast regions were evaluated in all patients. All patients underwent biopsy within 2 weeks of the study. Twenty patients were found to have a primary malignancy of the breast, whereas 10 had benign disease. The patients with breast carcinoma had surgery. Twelve patients had axillary lymph node metastases. Tc-99m MIBI breast imaging showed abnormal uptake in 18 of 20 malignancies and in 8 of 12 axillary lymph node metastases. Tc-99m tetrofosmin breast imaging showed abnormal uptake in 13 of 14 malignancies and in 6 of 10 axillary lymph node metastases. Sensitivity, specificity, and accuracy values obtained with Tc-99m MIBI and Tc-99m tetrofosmin scintigraphy for breast carcinoma were 90%, 90%, 90%, and 93%, 100%, 94%, respectively. The values obtained with Tc-99m MIBI and Tc-99m tetrofosmin scintigraphy for axillary lymph node metastases were 66%, 100%, 86%, and 60%, 100%, 76%, respectively. The authors conclude that both of these techniques are effective in the differentiation of malignant breast masses from benign ones and in detecting axillary lymph node metastases. However, Tc-99m tetrofosmin is superior to Tc-99m MIBI in detecting breast carcinoma.

Topics: Adult; Aged; Axilla; Breast Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Sestamibi

Breast cancer ranks the second position among the cancer of women in Japan. We report two cases of breast cancer detected by 99mTc-tetrofosmin. First case was 51 years old female with breast cancer (invasive papillotubular carcinoma) and dextrocardia. She received 99mTc-tetrofosmin myocardial scintigraphy to evaluate dextrocardia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy showed myocardium at the right side, gall bladder at the left lower side and abnormal uptake on the left chest wall. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed myocardium at the right side and abnormal uptake on the left chest wall. Second case was 78 years old female with breast cancer (intracystic papillary carcinoma) and arrhythmia. 99mTc-tetrofosmin myocardial scintigraphy was performed to evaluate arrhythmia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy shows hot nodule at the lateral side of the myocardium. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed abnormal uptake at the left lateral side on the chest wall. Both cases appeared illed foci as abnormal uptake with 99mTc-tetrofosmin scintigraphy, although histological diagnosis was different. We conclude that 99mTc-tetrofosmin scintigraphy is helpful for evaluating breast cancer.

Topics: Aged; Breast Neoplasms; Carcinoma, Papillary; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon

The aim of the study was to evaluate the possible role of scintimammography (SMM) with technetium-99m tetrofosmin in breast cancer. Thirty-three patients with breast disease and ten normal controls were included in the study. Planar scintigraphic images in supine anterior, prone lateral and lateral views, with the patient lying in lateral recumbency, were acquired. A qualitative analysis evaluating both breasts and lymph nodes was performed. All breast lesions were verified after surgery and/or by fine-needle aspiration. In 8 of the 33 patients, mammography was inconclusive because of mastectomy or dense breasts. For mammography, a sensitivity of 95.6%, a specificity of 66.7% and an accuracy of 89.6% were obtained. At SMM, 26 out of 28 malignant lesions (average size 2.8 cm, range 0. 4-12 cm), including two recurrences, were detected with a 92.8% sensitivity, a 100% specificity and a 95.1% accuracy. The smallest detectable carcinoma measured 0.6 cm. Two false-negative results on SMM were found in a 0.4-cm intraductal carcinoma and in the only mucinous papillary carcinoma in our series. With regard to lymph node analysis, 11 out of 12 axillary metastases (sensitivity=91.6%) were detected. A false-positive result, yielding a specificity of 92. 3% was also obtained. A metastatic involvement of the internal mammary chain was observed. No uptake was seen in 11 benign mammary lesions or at the level of the breast and axilla when neoplastic involvement was absent. In conclusion, SMM with 99mTc-tetrofosmin is an effective technique for the evaluation of primary breast carcinomas, recurrences and lymph node metastases.

Topics: Axilla; Breast; Breast Neoplasms; Case-Control Studies; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Sensitivity and Specificity

Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI), 99mTc-tetrofosmin and 99mTc-Q12 were all introduced for myocardial imaging but found additional applications as they are taken up by different tumours, enabling imaging of these lesions in patients. The aim of this study was to compare the uptake characteristics of these compounds in vitro in the human adenocarcinoma breast cell lines MCF-7 and ZR-75. It was shown that 99mTc-MIBI had the highest cellular uptake (15.9%+/-0.5% dose/mg protein after 60 min in MCF-7, and 14.2%+/-0.4% dose/mg protein in ZR-75), followed by 99mTc-tetrofosmin (6.8%+/-0.6% dose/mg protein in MCF-7, and 8. 2%+/-0.2% dose/mg protein in ZR-75) and 99mTc-Q12 (3.2%+/-0.1% dose/mg protein in MCF-7, and 3.5%+/-0.3% dose/mg protein in ZR-75 cells). For all three compounds tenfold differences in specific activity did not influence total cell-associated radioactivity. Uptake of 99mTc-MIBI and 99mTc-tetrofosmin was obviously lower at 4 degrees C than at 37 degrees C, whereas 99mTc-Q12 uptake showed only slight temperature dependence. When uptake was compared in cells grown to different cell densities (1 mg/ml cellular protein versus 0.3 mg/ml), no differences in uptake were detected when uptake was corrected for the amount of cellular protein present in the dishes. Furthermore, for all compounds it was shown that cellular radioactivity decreased rapidly after washing. Apart from the differences in cellular uptake of the three compounds after 60 min, no differences in residual cellular radioactivity after washing were found between the different compounds when expressed as a percentage of their 60-min uptake, suggesting that the efflux process of the radiolabelled compounds was similar. The differences in cell-associated activity after 60 min were thus presumably caused by differences in uptake. It was concluded that of the Tc-labelled compounds tested, 99mTc-MIBI had the highest cellular retention in both human breast tumour cell lines. However, for imaging in vivo not only radioactivity in the target organ is important, but also the ratio of radioactivity in the target versus that in the background. Therefore, further studies in vivo need to be performed to investigate which compound is the optimal imaging agent.

Topics: Adenocarcinoma; Breast Neoplasms; Female; Furans; Humans; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Time Factors; Tumor Cells, Cultured

The routine mammogram remains the procedure of choice for screening asymptomatic women for breast cancer. However, it accounts for an elevated percentage of misdiagnosed breast nodules particularly in younger women with dense breast tissue or fibrocystic disease. New radiopharmaceuticals including labelled monoclonal antibodies, thalium-201 and technetium-99m sestamibi are under investigation as possible solutions to this issue. 99mTc-tetrofosmin (Myoview), like 99mTc-sestamibi, is a lipophilic, cationic myocardial imaging agent. Mitochondrial membrane potential appears to play a significant role in the uptake and/or retention of 99mTc-tetrofosmin. Twenty-seven female patients with suspected breast cancer were included in the study. Twenty mCi of 99mTc-tetrofosmin were administered intravenously. Imaging was begun 10 min post-injection. In twenty-three patients, breast cancer was detected using 99mTc-tetrofosmin scintigraphy. Two carcinomas were missed. In two patients, both breast scintigraphy and intraoperative biopsies were negative. Our preliminary results suggest that this product may have a role in the differentiation of benign from malignant lesions, and were encouraging in terms of its potential usefulness as a marker of malignancy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Sensitivity and Specificity

The accumulation of 99mTc-tetrofosmin (TFos) was studied in wildtype (WT) and doxorubicin-resistant (AdrR) variants of the rat MatB and human MCF-7 breast tumor cell lines to determine whether TFos, like 99mTc-sestamibi (MIBI), is a substrate for P-glycoprotein (P-gp), a multidrug-resistance transporter.. The time course of accumulation of TFos and MIBI in WT and AdrR cells over 1 hr was studied using single-cell suspensions at 1 x 10(6) cells/ml incubated at 37 degrees C in the presence or absence of PSC833, a potent modulator of P-gp. Modulator dose-response curves were generated for PSC833, cyclosporin A, and verapamil.. In both MatB and MCF-7 cells, TFos and MIBI accumulated extensively in WT cells and accumulation was not affected by PSC833. In contrast, ADrR cell lines accumulated very little of either tracer, but addition of PSC833 or other modulator increased this accumulation in a dose-dependent fashion. TFos and MIBI did not differ significantly in their behavior.. TFos shares with MIBI the property of being a substrate for P-gp and thus TFos may be useful for functional imaging of tumor P-gp status.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Mammary Neoplasms, Experimental; Organophosphorus Compounds; Organotechnetium Compounds; Rats; Technetium Tc 99m Sestamibi; Time Factors; Tumor Cells, Cultured

Topics: Breast Neoplasms; Female; Humans; Lung Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging

Topics: Breast Neoplasms; Female; Humans; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging

Despite low specificity routine mammography is the method of choice to screen women for breast cancer. In addition high frequency ultrasonography (US) or magnetic resonance imaging (MRI) can improve breast cancer diagnosis. However there is a lack of conventional imaging to improve the high rate of false positive results that make biopsy or surgery necessary.. The purpose of our study was to evaluate prospectively the sensitivity, specificity, PPV and NPV of scintimammography with a new cationic complex Tc-99m-tetrofosmin.. Fourtyeight patients in whom mammography and/or high resolution ultrasonography (10 MHz) revealed suspicious breast lesions were studied with Tc-99m-tetrofosmin scintimammography. In thirtyfour of them biopsy and/or surgery was performed for histological evaluation. After intravenous injection of 555 MBq Tc-99m-tetrofosmin dynamic images over three minutes (1 frame/10 sec.) planar images in anterior and lateral projections (5 min. p.i.) and SPECT imaging including 3-D-reconstruction (20 min. p.i.) were performed. Scintimammography was evaluated as negative, equivocal (+), probably (+2) or definitely (+3) positive. Scintimammography with Tc-99m-tetrofosmin was negative in 18 patients (17 t.p., 1 f.n.) and positive in 16 patients (10 t.p., 6 f.p.). The false negative scintimammography was observed in a patient with infiltrating ductal carcinoma pT1, the false positive results in a patient with fibrocystic disease; all of the five fibroadenomas were also "false" positive. Sensitivity of Tc-99m-tetrofosmin scintimammography in this prospective study was 91%, specificity 74%, PPV 63% and NPV 94%. Scintimammographic results in patients with suspicious breast lesion show, that Tc-99m-tetrofosmin accumulates in breast cancer as well as in fibroadenoma. However the high NPV of 94% excludes breast cancer in suspicious mammographic lesions in a very high degree and therefore reduces the need of biopsy and/or surgery in most of these patients. Our first results show that scintimammography with Tc-99m-tetrofosmin might play a role as further diagnostic step before surgery for women in whom mammography and/or ultrasonography show suspicious lesions.

Topics: Adult; Aged; Breast; Breast Diseases; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Fibrocystic Breast Disease; Humans; Mammography; Middle Aged; Necrosis; Organophosphorus Compounds; Organotechnetium Compounds; Prospective Studies; Tomography, Emission-Computed, Single-Photon; Ultrasonography, Mammary

Myocardial SPECT imaging was performed with Tc-99m tetrofosmin. Intense focal uptake at the level of the left breast was observed. At mammography a breast carcinoma was suspected, which was confirmed after surgery. This may be the first report of neoplastic mammary uptake of Tc-99m tetrofosmin.

Topics: Breast Neoplasms; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon