sodium-pertechnetate-tc-99m and Breast-Neoplasms

Sentinel lymph node biopsy (SLNB) has become the gold standard for axillary staging. Debate remains as to the optimal method of SLN detection.. Determine whether patients undergoing an SLNB required the addition of isosulfan blue dye to radioisotope when an SLN was identified on a preoperative lymphoscintigram.. A prospective randomized controlled trial comparing the combination of radioisotope and blue dye versus radioisotope alone was performed between March 2010 and September 2012. The trial protocol was registered with Current Controlled Trials. Women with clinically and radiologically node-negative breast cancer with a positive preoperative lymphoscintigram were eligible for inclusion.. A total of 667 patients were included in the analysis with 342 patients receiving the combination (blue dye and radioisotope) and 325 patients receiving radioisotope alone. The groups were evenly matched both demographically and pathologically. The mean age was 48 years (48.3 vs 47.7 years; P = 0.47), the mean tumour size was 24.2 mm (24.3 mm vs 24.1 mm; P = 0.7) and there was no statistically significant difference in the grade of the tumors between the 2 groups (P = 0.58). There was no difference in the identification rate, nor was that in the number of nodes retrieved between the 2 groups (P = 0.30). There was no difference in the number of positive lymph nodes that were identified between the 2 groups (23.8% vs 22.1%; P = 0.64).. This study failed to demonstrate an advantage with the addition of isosulfan blue dye to radioisotope in the identification of the SLN in the presence of a positive preoperative lymphoscintigram.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Coloring Agents; Female; Humans; Lymphoscintigraphy; Mastectomy; Middle Aged; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Rosaniline Dyes; Sentinel Lymph Node Biopsy; Sodium Pertechnetate Tc 99m

We investigated a correlation between the expression of human sodium iodide symporter (hNIS) mRNA and the uptake of 99mTc-pertechnetate in 25 breast tumors. 99mTc-pertechnetate scintigraphy revealed positive uptake in 4 patients. The normalized mRNA expression of hNIS was higher in tumors with positive uptake on the scintigraphy (n=4, median 0.97, range 0.78-1.27) than that in negative uptake tumors (n=21, median 0.46, range 0.10-1.03, p < 0.005). 99mTc-pertechnetate uptake is correlated with the hNIS expression in the breast tumor.

Topics: Breast Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sodium Pertechnetate Tc 99m; Symporters

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

Topics: Adult; Antineoplastic Agents, Immunological; Biomarkers; Breast Neoplasms; Cardiac-Gated Imaging Techniques; Cardiotoxicity; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Reproducibility of Results; Risk Factors; Sodium Pertechnetate Tc 99m; Stroke Volume; Time Factors; Tomography, Emission-Computed; Trastuzumab; Treatment Outcome; Troponin I; Ventricular Dysfunction, Left; Ventricular Function, Left

Nuclear medicine with radioisotopes is extremely useful for clinical cancer diagnosis, prognosis, and treatment. Herein, polyethylene glycol (PEG)-modified nanoscale coordination polymers (NCPs) composed of hafnium (Hf

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Hafnium; Humans; Mice; Mice, Inbred BALB C; Particle Size; Polyethylene Glycols; Sodium Pertechnetate Tc 99m; Surface Properties; Tomography, Emission-Computed, Single-Photon

Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection.. To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques.. Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated.. In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe.. There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed.

Topics: Breast Neoplasms; Fiducial Markers; Intraoperative Period; Iodine Radioisotopes; Lymphatic Metastasis; Lymphoscintigraphy; Phantoms, Imaging; Radionuclide Imaging; Radiopharmaceuticals; Scattering, Radiation; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Aggregated Albumin; Treatment Outcome

Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in vivo is difficult to achieve. The goal was to develop a new highly sensitive and reliable preclinical longitudinal in vivo imaging model for this purpose, thereby facilitating discovery and validation of anticancer therapies or molecular imaging agents.. The strategy is based on breast cancer cells stably expressing the human sodium iodide symporter (NIS) fused to a red fluorescent protein, thereby permitting radionuclide and fluorescence imaging. Using whole-body nano-SPECT/CT with (99m)TcO4(-), we followed primary tumor growth and spontaneous metastasis in the presence or absence of etoposide treatment. NIS imaging was used to classify organs as small as individual lymph nodes (LNs) to be positive or negative for metastasis, and results were confirmed by confocal fluorescence microscopy. Etoposide treatment efficacy was proven by ex vivo anticaspase 3 staining and fluorescence microscopy.. In this preclinical model, we found that the NIS imaging strategy outperformed state-of-the-art (18)F-FDG imaging in its ability to detect small tumors (18.5-fold-better tumor-to-blood ratio) and metastases (LN, 3.6-fold) because of improved contrast in organs close to metastatic sites (12- and 8.5-fold-lower standardized uptake value in the heart and kidney, respectively). We applied the model to assess the treatment response to the neoadjuvant etoposide and found a consistent and reliable improvement in spontaneous metastasis detection. Importantly, we also found that tumor cells in different microenvironments responded in a heterogeneous manner to etoposide treatment, which could be determined only by the NIS-based strategy and not by (18)F-FDG imaging.. We developed a new strategy for preclinical longitudinal in vivo cancer cell tracking with greater sensitivity and reliability than (18)F-FDG PET and applied it to track spontaneous and distant metastasis in the presence or absence of genotoxic stress therapy. Importantly, the model provides sufficient sensitivity and dynamic range to permit the reliable assessment of heterogeneous treatment responses in various microenvironments.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; DNA Damage; Environment; Etoposide; Female; Fluorescence; Humans; Lymph Nodes; Microscopy, Confocal; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sodium Pertechnetate Tc 99m; Symporters; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Whole Body Imaging

The aim of the present study was to investigate the possible use of mouse double-minute 2 (MDM2) molecular imaging to predict chemotherapeutic sensitivity in breast cancer xenografts (BCXs). MCF-7 cells were transfected with MDM2 antisense oligonucleotides (ASONs), and MDM2 expression levels were determined by Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in MCF-7 cells transfected with ASONs and treated with paclitaxel. BCXs were established in nude mice by injection of ASONs, and tumor volumes were measured after paclitaxel treatment. MDM2 ASONs were labeled with 99mTc to generate an MDM2 molecular probe, and MDM2 expression levels were evaluated by imaging and Western blotting. MDM2 ASONs downregulated MDM2 expression in a dose-dependent manner and increased the rate of paclitaxel-induced cell growth inhibition. Imaging of tumors revealed significant differences in the tumor to skeletal muscle (T/M) ratio between groups. Tumor MDM2 protein expression was correlated with T/M ratios at 4 hours (R  =  .880) and 10 hours (R  =  .886). The effect of paclitaxel varied among nude mice bearing BCXs with different concentrations of ASONs, as shown by differences in tumor growth. MDM2 molecular imaging could be a promising method for predicting the sensitivity of BCXs to chemotherapy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Proliferation; Female; Heterografts; Humans; MCF-7 Cells; Mice; Mice, Nude; Neoplasm Transplantation; Oligonucleotides, Antisense; Paclitaxel; Proto-Oncogene Proteins c-mdm2; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m

Topics: Breast Neoplasms; Diphosphonates; Female; Humans; Middle Aged; Osteosarcoma; Radionuclide Imaging; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m

Topics: Breast; Breast Neoplasms; Female; Gamma Cameras; Humans; Magnetic Resonance Imaging; Nuclear Medicine; Practice Guidelines as Topic; Radionuclide Imaging; Societies, Medical; Sodium Pertechnetate Tc 99m

Some preparations of 99mTc-colloidal rhenium sulfide (Nanocis) contain excess free pertechnetate (99mTcO4) impurity (>5%).. To improve the radiochemical purity of Nanocis preparations and the quality of preoperative lymphoscintigraphy in sentinel node localization of breast cancer patients, we investigated the effects of temperature on the presence of free 99mTcO4 and nanocolloid size modification.. A Nanocis kit was reconstituted with sodium pertechnetate (650-850 MBq) in a final volume of 3.5 ml and heated for 30 min at 100, 115, or 130 degrees C. The radiochemical purity was determined by paper chromatography, in triplicate. The particle size was evaluated by membrane filtration through a 200-nm and 100-nm filter. The preoperative lymphoscintigraphy images were acquired about 2 h after tracer administration.. Significantly higher radiochemical purity values were observed with 28 Nanocis preparations heated at 130 degrees C (median: 99.8%, min-max: 97.0-99.9%) compared with values from 37 Nanocis preparations heated at 100 degrees C (median: 96.3%, min-max: 85.2-99.5%) or 26 Nanocis preparations heated at 115 degrees C (median: 95.1%, min-max: 85.7-99.8%). The interbatch variations of the radiochemical purity were reduced at 130 degrees C. A high temperature level (130 degrees C) did not modify the particle size. In lymphoscintigraphy, free 99mTcO4 uptake by the thyroid or stomach, which was sometimes observed with a Nanocis preparation heated at 100 or 115 degrees C, was never visualized with a Nanocis preparation heated at 130 degrees C.. These results indicate that increasing temperature from 100 to 130 degrees C can be used in routine clinical practice to improve the radiochemical purity of the Nanocis preparation.

Topics: Breast Neoplasms; Chlorides; Chromatography, Paper; Female; Filtration; Humans; Lymph Nodes; Lymphatic Metastasis; Particle Size; Radionuclide Imaging; Radiopharmaceuticals; Rhenium; Sodium Pertechnetate Tc 99m; Sulfides; Technetium Tc 99m Sulfur Colloid; Temperature

Topics: Aged, 80 and over; Breast Neoplasms; Diagnosis, Differential; Female; Goiter, Substernal; Humans; Sodium Pertechnetate Tc 99m; Thyroid Gland; Thyroid Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Ultrasonography

A murine, apoptosis-inducing monoclonal antibody (mTRA-8) targeting human DR5 was radiolabeled with Tc-99m. The binding affinity (K(d)) and the number of DR5 receptors were measured in MD MBA-231-derived 2LMP cell lines that were "sensitive" or "resistant" to mTRA-8 killing. Single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) evaluated the Tc-99m-mTRA-8 retention and distribution within xenograft tumors; biodistribution analyses confirmed the levels. Scatchard assays showed specific and high binding affinity of Tc-99m-mTRA-8 to DR5; the killing efficacy of mTRA-8 was unchanged by Tc-99m labeling. There was no significant difference between sensitive and resistant 2LMP cells for K(d) values (1.5 +/- 0.3 nmol/L = acid labile), or DR5 receptors (mean/cell = 11,000). SPECT/CT imaging analyses at 6 h after injection of Tc-99m-mTRA-8 revealed the second 1.5 mm shell from the surface of the mammary fat pad tumors (n = 5; 5,627 mm(3)) retained 12.7 +/- 1.4%ID/g, higher than the other shells, with no difference between the sensitive and resistant 2LMP tumors. Binding of Tc-99m-labeled mTRA-8 in tumor was specific; excess unlabeled mTRA-8 blocked Tc-99m-mTRA-8 retention in tumor by 45%. Retention of Tc-99m-labeled isotype antibody in tumor was consistent with the blocking study, and 30% lower. These studies show that SPECT/CT imaging provided detailed distribution information of Tc-99m-labeled mTRA-8 within breast tumor xenografts. Imaging could provide a mechanism to assess DR5 modulation when DR5 therapy is combined with chemotherapy and radiation, and thereby aid in optimizing the dosing schedule.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Humans; Immunoconjugates; Mice; Mice, Nude; Neoplasm Staging; Radioimmunodetection; Radiopharmaceuticals; Receptors, TNF-Related Apoptosis-Inducing Ligand; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Although the thyroid gland is the principal organ with the ability to concentrate iodide and take up Tc-99m pertechnetate, other tissues such as choroid plexus, salivary glands, mucoid cells of stomach, and lactating breast tissue also possess this property. The lactating mammary gland can concentrate iodide, which mediated by sodium/iodine symporter (NIS) is actively transported and secreted in the milk, to supply iodide to the newborn for the biosynthesis of thyroid hormones. The authors present an uncommon case of unilateral Tc-99m breast uptake in a breast-feeding woman.

Topics: Adult; Artifacts; Breast; Breast Neoplasms; False Positive Reactions; Female; Humans; Radionuclide Imaging; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Thyroid Neoplasms

Breast carcinomas express the Na(+)/I() symporter and may-albeit not a routine procedure-be imaged with (123)iodide ((123)I) and (99m)technetium-pertechnetate ((99m)TcO(4)(-)) scintigraphy. The aim of our prospective study was the comparison of (99m)TcO(4)(-)--and (123)I-single-photon emission computed tomography (SPECT) with (18)F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in patients suspicious for breast cancer.. Twenty-nine (29) untreated patients suspected of having breast carcinoma were prospectively examined with thorax SPECT with (99m)TcO(4)(-) (n=19) or (123)I (n=10), respectively, and FDG-PET (n=29) prior to biopsy. Tumor-to-background ratios (TBRs) were calculated for SPECT findings. Mean and maximum standardized uptake values (SUVs) were calculated for PET findings. Findings were compared in an intra-individual lesion-to-lesion analysis.. In 28 of 29 patients, malignancy was verified with histopathology. In imaging the primary tumor, sensitivities of (99m)TcO(4)(-)-SPECT, (123)I-SPECT, and FDG-PET were 63%, 67%, and 89%, respectively. TBR maximum was 2.6+/-1.1 in (99m)TcO(4)()-SPECT and 2.3+/-0.6 in (123)I-SPECT. In FDG-PET, mean tumor SUV was 4.1+/-4 and maximum tumor SUV was 5.4+/-5.1. In contrast to FDG-PET, (99m)TcO(4)()-SPECT was ineffective in imaging nodal and distant metastases in the thorax, and (123)I-SPECT failed in imaging lymph node infiltrations. Distant metastases were not present in patients of the (123)I group, and the value of (123)I-SPECT was not evaluated.. In contrast to FDG-PET, (99m)TcO(4)(-) and (123)I-SPECT are ineffective in imaging breast carcinoma in clinical practice.

Topics: Adult; Aged; Breast Neoplasms; False Negative Reactions; Female; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Positron-Emission Tomography; Prone Position; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Supine Position; Thoracic Neoplasms; Tomography, Emission-Computed, Single-Photon

In order to depict the anatomy and improve the localization, sentinel node scintigraphy in breast cancer was combined with intravenous administration of pertechnetate. As this may reduce the detectability of weak 'hot spots', the number of lymph nodes detected at scintigraphy and at surgery in one group of patients was compared with that obtained in another group that had not received pertechnetate.. The number of 'hot spots' at frontal and lateral views in 47 female patients at scintigraphy performed 2-3 h after subcutaneous injection of radiocolloid together with 25 MBq pertechnetate i.v. was compared in retrospect with that of 41 female patients who had not received pertechnetate. The number of lymph nodes detected at surgery using a hand-held gamma probe together with blue dye in the two groups was also compared. The washout kinetics of pertechnetate was studied in 10 patients.. There was no difference in the number of detected lymph nodes at any comparison. The kinetics study revealed a decreasing activity with time after correction for physical decay.. Administration of a 25 MBq pertechnetate i.v. in order to improve the anatomical localization at sentinel node scintigraphy in breast cancer does not reduce the detectability of radioactive lymph nodes.

Topics: Adult; Aged; Breast Neoplasms; Coloring Agents; Female; Gamma Cameras; Humans; Lymph Nodes; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies; Sentinel Lymph Node Biopsy; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Aggregated Albumin

Sodium iodide symporter (NIS) is a molecule involved in active accumulation of iodine in thyroid gland for the biosynthesis of thyroid hormone. Its expression has also been demonstrated in extra-thyroidal tissues including lactating mice mammary gland and also in human breast cancers. Iodide transport in thyroid cells through NIS is the basis for using radioiodine for diagnosis and treatment of differentiated thyroid carcinoma. The similar approach may prove beneficial for the diagnosis and treatment of breast cancer if iodine uptake, its retention and NIS expression can be shown unequivocally in malignant tumors. The aim of the present study was to investigate NIS expression, in vivo iodine transport ability and fate of iodine in human breast tumors. Women (age 33-58 years) with infiltrating duct carcinoma confirmed by FNAC and subsequent histopathology were the subject of this study. Expression of NIS RNA and protein was confirmed by RNAase protection assay, western blot and immunohistochemistry respectively in surgically excised breast tumor tissue. Iodine transport ability and its nature was assessed both in vivo and in vitro. We report high NIS expression at both transcriptional and translational level and its ability to transport iodine in human breast tumors. The in vivo iodine transport ability was confirmed by scintigraphy. Unlike thyroid, perchlorate and thiocyanate do not inhibit iodine transport in breast tumors. The presence of iodinated proteins suggests the longer retention time. The unequivocal demonstration of NIS expression, its functionality and retention of iodine by organification further provides supportive evidence for use of radioiodine as an additional treatment modality of human breast carcinoma.

Topics: Adult; Blotting, Western; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Immunohistochemistry; In Vitro Techniques; Iodine; Iodine Radioisotopes; Middle Aged; Nuclease Protection Assays; Radionuclide Imaging; Radiopharmaceuticals; RNA; Sodium Pertechnetate Tc 99m; Symporters

Bombesin-like peptides are neurotransmitters and cancer growth factors. Several tumors, breast cancer among them, show one or more than one of the three known bombesin receptors. We have synthesized and labeled with technetium 99m a new pentadecapeptide, analogue to the leu13 amphibian bombesin (99mTc BN). Labeling yield was 83 +/- 4%. Prone Scintimammography was performed on five patients affected by breast cancers (T categorization: two T1b and three T1c), after injecting 0.7 mg, 185 to 296 MBq (5 to 8 mCi) of the peptide. Total body scan did not show free technetium biodistribution. No adverse reaction was observed. Prone Scintimammography with 99mTc Sestamibi (99mTc SM) was also performed few days later. 99mTc BN detected all 5 cancers, whereas 99mTc SM only four: all the T1c and one T1b cancer. Two of them showed axillary node invasion that was detected by both the radiotracers. A fibroadenoma present on contralateral breast to the one with cancer, was not detected neither by 99mTc SM nor by 99mTc BN. Tumor/breast normal tissue ratio (T/B) was constantly higher with 99mTc BN than with 99mTc SM. Maximal T/B was measured as 1.79 with 99mTc SM and 2.25 with 99mTc BN 5 min after fast i.v. administration. In conclusion our 99mTc BN is taken up by primary breast cancer showing higher T/B than 99mTc SM (p < 0.01). In our limited scale, 99mTc BN appears to be safe and, in our limited scale, even more accurate than 99mTc SM for detecting breast cancer.

Topics: Aged; Bombesin; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Peptides; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Sestamibi

The use of antibodies as targeting agents for the delivery of radioisotopes to tumors is a promising concept that has received widespread attention since the advent of monoclonal antibody (mAb) technology. The following studies are described in this article: the 99mTc-randiolabeling of 2-iminothiolane (2-IT) modified antibodies and 6-p-isothiocyanatobenzyl- diethylene-triamine penta-acetic acid (CITC-DTPA) immunoconjugates of anti-EGF-receptor antibodies murine ior egf/r3 and humanized h-R3; the analytical methods for quality control of the radiopharmaceutical such as instant thin layer chromatography-silica gel (ITLC-SG); the biological assessment of the radiolabeled molecule using flow cytometry analysis; in vitro stability studies with cysteine and DTPA challenge and the biodistribution studies in 4NMRI xenografted nude mice with U-87 human glioblastoma multiforme and MDA-MB-468 breast cancer cell lines. Labeling efficency of (96.48 +/- 0.70%) (98.42 +/- 0.38%), (94.8 +/- 1.25%) and (96.41 +/- 0.89%) was achieved for 99mTC-2-IT ior efg/r3, 99mTc-CITC-DTPA- ior egf/r3, 99mTc-CITC-DTPA- h-R3 and 99mTc-DIACIM h-R3, respectively. Radiocolloids were less than 2.0% in all cases. The biological activity measured by flow cytometry analysis using the MDA-MB-468 breast cancer cell line showed an immunoreactivity fraction greater than 85% in all concentrations of each immunoconjugate. Challenge studies demonstrated no evidence of transcomplexation of 99mTc to 1.0 mM DTPA for 2-IT modified antibody ior egf/r3 and CITC-DTPA immunoconjugates and only 8.7%, 4.9% and 5.0% of the 99mTc-radiolabeled was transcomplexed to 1.0 mM cysteine after 1 h incubation at 37 degrees C for 2-IT modified antibody ior egf/r3, CITC-DTPA ior egf/r3 and CITC-DTPA h-R3, respectively. Biodistribution studies with 2-IT modified antibodies and CITC-DTPA immunoconjugates indicated high tumor uptake in both cell lines with both immunoconjugates and no accumulation of the radiolabeled antibodies in normal organs.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Breast Neoplasms; Central Nervous System Neoplasms; Colonic Neoplasms; Cross-Linking Reagents; Disease Models, Animal; ErbB Receptors; Glioblastoma; Humans; Imidoesters; Immunoconjugates; Immunoglobulin G; Immunoradiometric Assay; Isothiocyanates; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Pentetic Acid; Sodium Pertechnetate Tc 99m; Tissue Distribution; Tumor Cells, Cultured

Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Erythrocytes; Female; Gated Blood-Pool Imaging; Heart; Humans; Middle Aged; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Technetium

Recent data suggest that somatostatin receptors (SSTRs) are expressed on various tumor cells. High-level expression of SSTR on the tumor cell surface provides the basis for the successful clinical use of radiolabeled ligands for the in vivo localization of tumor sites. We have characterized the in vitro binding properties of the novel SSTR ligand 99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5. 99mTc-P829 bound to primary tumor cells and tumor cell lines with high affinity and high capacity. The dissociation constants (Kd) ranged between 1 and 20 nM. 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd, 2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM). Binding of 99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3-octreotide (IC50, 20 nM). In contrast, the binding of 99mTc-P829 to hSSTR2 and hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr3-octreotide but not by VIP. 99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic tumor sites in seven of eight patients with breast cancer and six of six patients with melanoma. In summary, our data show that 99mTc-P829 binds with high affinity to many different types of primary and cloned tumor cells. Furthermore, our data identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target receptors. Because these receptors are frequently expressed at high levels on primary tumor cells, 99mTc-P829 appears to be a promising novel peptide tracer for tumor imaging.

Topics: Animals; Binding, Competitive; Blotting, Northern; Breast Neoplasms; COS Cells; Female; Humans; Melanoma; Neoplasms; Peptides, Cyclic; Radioligand Assay; Receptors, Somatostatin; RNA, Messenger; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed, Single-Photon; Tumor Cells, Cultured

After the intravenous administration of a radiolabeled somatostatin analogue (octreotide), normal thyroid and neoplastic and nonneoplastic thyroid lesions can be visualized. The authors present the cases of two patients who underwent somatostatin receptor scintigraphy (SSRS) using In-111 pentetreotide: one for the study of suspected paraneoplastic ACTH hypersecretion, and the other for a restaging of breast carcinoma with neuroendocrine features. In both patients, SSRS revealed increased uptake in the thyroid, corresponding to "cold" nodules on Tc-99m pertechnetate imaging. Cytologic and histologic examinations showed the typical features of thyroid goiters without lymphocytic infiltration.

Topics: Adenoma; Adrenocorticotropic Hormone; Biopsy, Needle; Breast Neoplasms; Carcinoma; Female; Goiter, Nodular; Humans; Indium Radioisotopes; Injections, Intravenous; Middle Aged; Neoplasm Staging; Neuroendocrine Tumors; Paraneoplastic Syndromes; Pituitary Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Sodium Pertechnetate Tc 99m; Somatostatin; Thyroid Gland; Thyroid Nodule

Topics: Antineoplastic Agents; Breast; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Microspheres; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Aggregated Albumin; Tomography, Emission-Computed

Over a period of twelve years we have performed 793 parasternal lymphoscintigrams with microcolloids in 272 patients with unilateral carcinoma of the breast. In 173 patients we were able to follow their course with an average of four examinations and an average period of observation of 48 months. The parasternal lymph nodes could be identified in 59.6% (on the side of the tumour in 55.1%, on the contralateral side in 64.2%). Expressed as an index with maximal value of 1, the (non-)demonstration constant was 0.79 (side of the tumour 0.78, opposite side 0.80). Comparison of the total scans with the initial findings showed general loss of scintigraphic uptake which, however, is not reflected during individual ICR localisation. Patients with the highest prevalence of parasternal metastases showed atypical uptake. There was no change in uptake in those patients who subsequently developed distant metastases.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Colloids; Female; Follow-Up Studies; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Radionuclide Imaging; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Sternum; Time Factors

A procedure for obtaining microcirculation coefficient is described. It is based on the phenomenon of formation of a focus of radionuclide hyperfixation on scintigrams of tumor area due to embolization of its arterioles and precapillaries with radionuclide. The method was used in 26 breast cancer patients before neoadjuvant chemotherapy. A direct correlation between the microcirculation coefficient and degree of tumor-induced pathomorphosis of tumor cells was established. The coefficient values proved more or less predictive of tumor response to chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Drug Evaluation; Embolization, Therapeutic; Female; Fluorouracil; Humans; Microcirculation; Middle Aged; Prognosis; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Time Factors

Both geometrical isomers (E and Z) of an aminotamoxifen (2) have been prepared as precursors of the corresponding E and Z iodotamoxifens (1). The ability of E and Z-1 and 2 to compete with [3H]estradiol for estrogen receptors in rat uterine cytosol was measured relative to Z-tamoxifen and estradiol. The four tamoxifen derivatives showed affinities ranging from 50% to 1600% of that of tamoxifen. Under the same conditions, tamoxifen's relative binding affinity was 0.2% of that of estradiol. Preparative routes to the radioiodo-tamoxifens, [131I]-E and Z-1, were also developed and provided approximately 100 MBq of 'no carrier added' material in 40-60% radiochemical yield. Study of the biodistribution of these radioligands in tumor-bearing mice demonstrated significant radioactivity in the tumors and in the uterus. For [131I]-E-1, target to background ratios reached 28 for uterus/blood and 10 for tumor/blood; corresponding optimum ratios for [131I]-Z-1 were 10 and 5. A washout study using estradiol indicated selective uptake in the uterus of Swiss white mice. However, tumor uptake and image contrast in humans following intravenous administration of either [131I]-E or Z-1 were insufficient to allow diagnostic use of the radioiodotamoxifens.

Topics: Aged; Animals; Breast Neoplasms; Female; Humans; In Vitro Techniques; Iodine Radioisotopes; Isomerism; Lung; Mice; Mice, Inbred C3H; Middle Aged; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Receptors, Estrogen; Sodium Pertechnetate Tc 99m; Tamoxifen; Tissue Distribution; Uterus

Topics: Adult; Breast Neoplasms; Extravasation of Diagnostic and Therapeutic Materials; Female; Heart Aneurysm; Humans; Lactation; Radionuclide Imaging; Sodium Pertechnetate Tc 99m

The authors propose a radionuclide method of diagnosis of breast tumors based on focal radiometry of 99mTc-pertechnetate accumulated in them after injection. Radiometry is done with a scanner with a pulse counter. The ratio of pulse counts accumulated in a tumor, to this indicator on the contralateral side makes it possible to determine a tumor type. This method is of diagnostic importance for tumors with a diameter less than 2 cm, their individual sections and also for lymph nodes.

Topics: Breast Neoplasms; Female; Humans; Middle Aged; Radiometry; Sodium Pertechnetate Tc 99m

Cavernous hemangiomas are the commonest benign tumors of the liver. Unfortunately, neither US nor CT allows cavernous hemangiomas to be positively discriminated from more dangerous lesions, e.g. metastases. Blood-pool scintigraphy has been reported to be a reliable technique for diagnosing hemangiomas of the liver: in fact, among the liver lesions in which 99m Tc-red blood cells gradually accumulate, only hemangiomas present an increased accumulation of radiotracers as soon as 2 hours afterwards. To determine the present value of blood-pool scintigraphy in oncological patients, we studied 17 patients whose US staging had shown dubious focal liver lesions. This technique allowed one or more hemangiomas to be diagnosed in 15 cases, and metastatic lesions in 2 cases. Scintigraphy with 99m Tc-labelled red blood cells proves thus to be an accurate method for the identification of cavernous hemangiomas of the liver in case of dubious US findings.

Topics: Breast Neoplasms; Erythrocytes; Female; Hemangioma, Cavernous; Humans; Liver; Liver Neoplasms; Neoplasm Staging; Neoplasms, Multiple Primary; Radionuclide Imaging; Sodium Pertechnetate Tc 99m

Computerized emission tomography of the brain is an atraumatic and highly informative technique for diagnosis of metastatic brain tumours. The above method is of major practical significance as a primary test in diagnosing metastases in the brain in cases of clinical neurological symptom complex.

Topics: Brain; Brain Neoplasms; Breast Neoplasms; Female; Humans; Lung Neoplasms; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed; Tomography, X-Ray Computed

The purpose of this study was to determine what effect further improvement in an Anger camera's intrinsic resolution has on lesion detection. We studied 52 patients undergoing bone imaging and 58 undergoing liver imaging. All patients had images performed in rapid sequence on ZLC -75 and ZLC -37 Anger cameras, both by Siemens. The two imaging systems are virtually identical except for the number of photomultiplier tubes and crystal thickness; these resulted in differences in intrinsic resolution ( ZLC -75 less than 3.8 mm FWHM at 140 keV, ZLC -37 less than 4.9 mm) and sensitivity ( ZLC -75 approximately 0.91 of ZLC -37 at 140 keV). Observer performance, measured by ROC curves, for detection of abnormalities was virtually identical with the two instruments. Subjectively, there was a trend toward preference of the ZLC -75 images, but this was not associated with any significant improvement in lesion detectability even in the subgroup in which a preference for one or the other instrument was noted.

Topics: Bone and Bones; Breast Neoplasms; Female; Humans; Image Enhancement; Liver; Lung Neoplasms; Male; Prostatic Neoplasms; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Sulfur; Technetium; Technetium Tc 99m Sulfur Colloid

Topics: Adult; Aged; Breast Diseases; Breast Neoplasms; Female; Humans; Mammography; Middle Aged; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Thermography; Tomography, X-Ray Computed; Ultrasonography