technetium-tc-99m-tetrofosmin and Neoplasms

This review aims at fostering comprehension and knowledge not only for expert physicians who can skillfully handle various techniques for tumor imaging but also for young practitioners in the field of nuclear medicine. As image processing software and hardware become smaller, faster and better, SPECT will adapt and incorporate these advances. A principal advantage of SPECT over PET is the more widespread availability of the equipment and lower cost for the introduction of the system in community-based facilities. Moreover, SPECT has become less dependent on a limited number of acknowledged experts for its interpretation owing to a variety of handy computer tools for imaging analyses. The increasing use of PET in tumor imaging is not necessarily proportional to the decline of SPECT. General physicians' attention to SPECT technology would also increase more by evoking their interest in "tracer imaging."

Topics: Animals; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Sestamibi; Technology Assessment, Biomedical; Thallium; 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

Little is known about the affinity and stability of. In vesicles,

Topics: Animals; Cell Line, Tumor; Drug Monitoring; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Stability; Female; Humans; Liver; Mice, SCID; Molecular Imaging; Multidrug Resistance-Associated Proteins; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Propionates; Quinolines; Radiopharmaceuticals; Time Factors; Verapamil; Xenograft Model Antitumor Assays

To measure the organ dose and calculate effective dose from CT attenuation correction (CTAC) acquisitions from four commonly used gamma camera single photon emission CT/CT systems.. CTAC dosimetry data was collected using thermoluminescent dosemeters on GE Healthcare's Infinia™ Hawkeye™ (GE Healthcare, Buckinghamshire, UK) four- and single-slice systems, Siemens Symbia™ T6 (Siemens Healthcare, Erlangen, Germany) and the Philips Precedence (Philips Healthcare, Amsterdam, Netherlands). Organ and effective dose from the administration of (99m)Tc-tetrofosmin and (99m)Tc-sestamibi were calculated using International Commission of Radiological Protection reports 80 and 106. Using these data, the lifetime biological risk was calculated.. The Siemens Symbia gave the lowest CTAC dose (1.8 mSv) followed by the GE Infinia Hawkeye single-slice (1.9 mSv), GE Infinia Hawkeye four-slice (2.5 mSv) and Philips Precedence v. 3.0. Doses were significantly lower than the calculated doses from radiopharmaceutical administration (11 and 14 mSv for (99m)Tc-tetrofosmin and (99m)Tc-sestamibi, respectively). Overall lifetime biological risks were lower, which suggests that using CTAC data posed minimal risk to the patient. Comparison of data for breast tissue demonstrated a higher risk than that from the radiopharmaceutical administration.. CTAC doses were confirmed to be much lower than those from radiopharmaceutical administration. The localized nature of the CTAC exposure compared to the radiopharmaceutical biological distribution indicated dose and risk to the breast to be higher.. This research proved that CTAC is a comparatively low-dose acquisition. However, it has been shown that there is increased risk for breast tissue especially in the younger patients. As per legislation, justification is required and CTAC should only be used in situations that demonstrate sufficient net benefit.

Topics: Female; Humans; Incidence; Male; Middle Aged; Myocardial Perfusion Imaging; Neoplasms; Netherlands; Organophosphorus Compounds; Organotechnetium Compounds; Radiometry; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Thermoluminescent Dosimetry; Tomography, X-Ray Computed

The multidrug resistance (MDR) phenotype is frequently associated with the overexpression of transmembrane drug proteins such as the P-glycoprotein (Pgp) and/or multidrug resistance related protein-1 (MRP1). These proteins belong to the superfamily of the so-called ATP-binding cassette superfamily and act as drug efflux pumps of a broad range of chemotherapeutic agents commonly used in the treatment of malignancies. These proteins have been found to be overexpressed in both haematological and solid tumours and are considered as adverse prognostic factors. The ability to obtain in vivo and non-invasively information regarding the functional activity of MDR-related transporters, using probes that mimic the antineoplastic agents, provide a very useful tool in the clinical setting by determining the individual tumour susceptibility to chemotherapy. This previous knowledge could serve as a critical tool for optimizing chemotherapeutic protocols on a patient-specific basis. The emergence of non-invasive molecular imaging techniques using radiolabelled probes provides an interesting approach for functional assessment of the classical mechanism of MDR in cancer patients. Toward this objective, the clinically approved 99mTc-labelled cationic lipophilic complexes (sestamibi and tetrofosmin) have been characterized as transport substrates of Pgp and MRP1 and proposed as surrogate markers of chemotherapeutic agents for functional evaluation of MDR by single-photon emission tomography (SPECT). Here we review the potential applications of these agents in identifying drug resistance mechanisms based on functional assays and their potential as a tool for evaluating the efficacy of MDR inhibitors, using cellular and animal models of chemoresistance.

Topics: Animals; ATP-Binding Cassette Transporters; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Mice; Multidrug Resistance-Associated Proteins; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; ROC Curve; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon

The biologic and microenvironmental factors determining (99m)Tc sestamibi (MIBI) and (99m)Tc tetrofosmin (TF) uptake in breast tumors are incompletely understood, especially in P-glycoprotein (Pgp)-negative tumors. We analyzed the influence of glucose administration on the uptake and retention of MIBI and TF in Pgp-negative tumor-bearing mice in vivo. Twenty (20) mice bearing Ehrlich ascites tumor cell (EATC) xenografts were divided into four groups: (1) MIBI, (2) MIBI+glucose, (3) TF, and (4) TF+glucose. Glucose was administered (5.0 g/kg body weight) intraperitoreally (i.p.) 1 hour before scintigraphy. There were significant differences between the E-UPR MIBI and MIBI+glucose groups (p = 0.009) and minor differences in L-UPR between these groups (p = 0.04). There was a significant inverse correlation between E-UPR of MIBI and glucose levels (r = 0.71, p = 0.02). Comparing the four groups, the highest E-UPR was obtained in the MIBI group (p = 0.006). Other parameters were not different in the MIBI and MIBI+glucose groups and in the TF and TF+glucose groups. Increased blood glucose level affected the MIBI uptake of tumor tissue, particularly for E-UPR. We suggest that these findings were due to basically decreased blood flow and secondarily decreased extracellular pH. However, glucose administration did not affect TF.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blood Glucose; Carcinoma, Ehrlich Tumor; Data Interpretation, Statistical; Female; Glucose; Metabolism; Mice; Mice, Inbred BALB C; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Sestamibi

It has been postulated that radiopharmaceuticals can be used to predict the therapeutic response to (chemo)therapy, which could lead to individualized treatment regimens. In this study, 18F-deoxyglucose, 99mTc-tetrofosmin, 125I-deoxyuridineribose, and 125I-methyltyrosine were tested for this purpose.. The uterine sarcoma cell line MES-SA (MDR-) and its multidrug resistant variant, MES-SA/Dx5 (MDR+), were used. The MDR+ cells express high levels of P-glycoprotein, which makes them relatively resistant to various chemotherapeutic agents. Cells were cultured in the presence of escalating concentrations of doxorubicin, and the cellular uptake of the radiopharmaceuticals was determined.. Decreasing 18F-deoxyglucose uptake at escalating doxorubicin concentrations reflected the chemosensitivity of the cells: 18F-deoxyglucose uptake in the MDR- cells was reduced to 40% of the baseline level in the presence of 1 microM of doxorubicin, compared to 74% in the MDR+ cells. The 125I-deoxyuridineribose uptake in MDR- cells was reduced to 2% of the baseline level when cultured at a concentration of 1 microM of doxorubicin, while this was 79% in the MDR+ cells. The same trend was observed with 125I-methyltyrosine. The enhanced doxorubicin chemosensitivity of MDR+ cells in the presence of verapamil, a modulator of P-glycoprotein, was reflected by the reduced uptake of 18F-deoxyglucose, 125I-deoxyuridineribose, and 125I-methyltyrosine. Furthermore, baseline 99mTc-tetrofosmin uptake in MDR+ cells was more than six-fold lower than in MDR- cells.. In the presence of doxorubicin, the uptake of 18F-deoxyglucose, 125I-deoxyuridineribose and, to a lesser extent, 125I-methyltyrosine is more pronouncedly reduced in MDR- cells than in MDR+ cells. The reversal of doxorubicin-resistance of MDR+ cells by verapamil was also reflected by the uptake of 18F-deoxyglucose, 125I-deoxyuridineribose, and 125I-methyltyrosine. 99mTc-tetrofosmin uptake reflected P-glycoprotein expression without exposure to doxorubicin.

Topics: DNA; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Fluorodeoxyglucose F18; Humans; Idoxuridine; Iodine Radioisotopes; Male; Methyltyrosines; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Verapamil

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

Sestamibi, tetrofosmin, and furifosmin are 99mTc-labeled myocardial perfusion imaging agents which have been shown to be substrates for P-glycoprotein (Pgp), the multidrug-resistance transporter which is overexpressed in some tumors. The three tracers were directly compared in vitro in the human breast cancer cell line MCF7-WT and two multidrug-resistant variants, MCF7-BC19 (MDR1 gene transfected) and MCF7-AdrR (doxorubicin selected). Tracer accumulation over the course of 60 minutes was determined. Dose-response curves were generated for two modulators of Pgp function, GG918 and PSC833. The general shape of accumulation curves for the three tracers in MCF7-WT cells was similar, with accumulation levels being sestamibi > tetrofosmin > furifosmin. Accumulation of sestamibi and furifosmin in MCF7-BC19 cells was reduced to 10% and 21% of MCF7-WT levels, respectively, but this accumulation deficit could be completely reversed by addition of 0.1 microM GG918 or 2 microM PSC833. Accumulation of sestamibi and tetrofosmin in MCF7-AdrR cells was 1.6% and 12% of MCF7-WT levels, respectively, and could only be enhanced to 30% and 45% of MCF7-WT levels by addition of GG918 or PSC833. In contrast, furifosmin showed similar levels of accumulation in MCF7-WT and MCF7-BC19 cells, slightly lower levels in MCF7-AdrR cells, and no consistent response to Pgp modulators. These results support the continued investigation of sestamibi and tetrofosmin as agents for functional imaging of multidrug resistance in human cancer.

Topics: Acridines; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cyclosporins; Drug Resistance, Neoplasm; Furans; Humans; Isoquinolines; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Technetium Tc 99m Sestamibi; Tetrahydroisoquinolines; Tomography, Emission-Computed, Single-Photon; Tumor Cells, Cultured

Tc-99m-tetrofosmin SPECT was performed on 6 occasions in 4 patients with hypopharyngeal carcinoma, lung carcinoma, esophageal carcinoma and maxillary plasmocytoma and compared with Tl-201 SPECT. All lesions accumulated both Tc-99m-tetrofosmin and Tl-201. Early uptake ratios of Tc-99m-tetrofosmin were about 2 but those of Tl-201 were much higher (more than 3). Washout rates of Tc-99m-tetrofosmin were higher than those of Tl-201. There was a good positive correlation between the early uptake ratio of Tc-99m-tetrofosmin and that of Tl-201. The delayed uptake ratio and washout rate showed poor correlation. In conclusion, early uptakes of both the agents were similar but their retention patterns were different. Tc-99m-tetrofosmin may be used for tumor imaging though more studies are required to evaluate diagnostic accuracy and the significance of delayed images.

Topics: Aged; Esophageal Neoplasms; Female; Humans; Hypopharyngeal Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maxillary Sinus Neoplasms; Metabolic Clearance Rate; Middle Aged; Neoplasms; Organophosphorus Compounds; Organotechnetium Compounds; Plasmacytoma; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon