sodium-pertechnetate-tc-99m and Melanoma

Topics: Bleomycin; Chlormerodrin; Eye Neoplasms; Gallium Radioisotopes; Humans; Melanoma; Mercury Radioisotopes; Methods; Orbital Neoplasms; Phosphorus Radioisotopes; Radionuclide Imaging; Selenomethionine; Serum Albumin, Radio-Iodinated; Sodium Pertechnetate Tc 99m; Technetium

Accurate staging and early detection of metastases are crucial to melanoma management. It would thus be of great value to have a widely available, cost-effective method that allows to examine the whole body and is more specific than current imaging modalities.. The purpose of the study was to assess the value of immunoscintigraphy with 99mTc-radiolabeled F(ab')2 fragments of the 225.28S monoclonal antibody in the staging of melanoma.. 29 patients with known or suspected metastases were enrolled in the study and examined by monoclonal antibody fragment scintigraphy. The results were compared to physical examination, other imaging modalities and, where available, histology.. Antibody scintigraphy detected 9/34 metastases. There were 2 false-positive lesions. Diagnostic accuracy was 41%, sensitivity 26% and specificity 83%.. 99mTc-radiolabeled F(ab')2 monoclonal antibody-fragment scintigraphy cannot be recommended for staging of melanoma patients. The search for more sensitive radiopharmaceuticals for scintigraphy should thus be encouraged.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Neoplasm; False Positive Reactions; Female; Humans; Immunoglobulin Fab Fragments; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Predictive Value of Tests; Radioimmunodetection; Sensitivity and Specificity; Skin Neoplasms; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed, Single-Photon

A total of 493 melanoma patients were investigated by 20 European nuclear medicine departments by means of the same 99mTc-labelled immunoradiopharmaceutical and the same immunoscintigraphy (ISG) protocol. (i) No chemical or clinical toxicity was detected during or following the studies. (ii) Positive results were obtained in 287/363 (79%) patients (321 carrying known lesions and 42 carrying previously occult lesions): in 231 (80%) of them, 402/402 lesions were imaged; in the remaining 56 ISG-positive patients, 108/204 lesions were imaged; in 76 patients 0/122 lesions were imaged. (iii) The fraction of melanoma lesions visualized by ISG was 510/728 (70.1%); 605 of these lesions were already documented at the time of the study, and 123 were previously occult. (iv) A total of 218 documented melanoma lesions (30%) were not visualized by ISG in 132 patients: about 70% of the ISG-negative lesions were of small size (less than 2 cm diameter). (v) The melanoma nature of 69/123 previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The results obtained in this study are similar to those obtained in the Italian Multicentre Study which had previously been carried out with 258 melanoma patients.

Topics: Antibodies, Monoclonal; Europe; Humans; Immunoglobulin Fab Fragments; Isotope Labeling; Melanoma; Multicenter Studies as Topic; Radionuclide Imaging; Skin Neoplasms; Sodium Pertechnetate Tc 99m

Topics: Humans; Melanoma; Radionuclide Imaging; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Thyroid Neoplasms; Thyroid Nodule; Time Factors

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

The aim of this investigation was to test for the scintigraphic detection of metastases of malignant melanoma with a new radiopharmaceutical, 99Tcm-glutathione (99Tcm-GSH), in comparison with 99Tcm-anti-melanoma antibody (99Tcm-AMAb). Glutathione was labelled with 99Tcm by a Sn2+ reduction method with an efficiency of > 99% as determined by instant thin layer chromatography (ITLC). Anti-melanoma antibody was obtained as a kit from SORIN (Italy) and labelled with 99TcmO-4. Forty-three patients with a total of 55 biopsy-proven metastatic melanoma foci, 1 ocular melanoma and 20 benign pathologic foci, also confirmed by ultrasound, computed tomography and magnetic resonance imaging, were included in the study after giving their informed consent. Following the intravenous (i.v.) injection of 500 MBq 99Tcm-AMAb, scintigraphic images of the involved areas were obtained 6 h post-injection. Three days later, the same patients were given 500 MBq 99Tcm-GSH i.v. and images were obtained 6 and 24 h post-injection. The images were classified as positive (focal abnormal accumulation) or negative. Quantitative evaluation was also applied. Regions of interest were drawn over the involved areas and nearby soft tissues and the target-to-nontarget (T/NT) ratios obtained with 99Tcm-AMAb (T/NT: 1.92 +/- 0.2) and 99Tcm-GSH (T/NT: 1.84 +/- 0.2) were compared (0.1 < P < or = 0.3). The sensitivity (and specificity) of 99Tcm-AMAb and 99Tcm-GSH in the detection of malignant melanoma metastases were 91% (95%) and 84% (90%), respectively. Compared with 99Tcm-AMAb, the advantages of 99Tcm-GSH are lower levels of blood radioactivity, lower costs and easy in-house preparation. In conclusion, our results show that 99Tcm-GSH is a potentially useful radiopharmaceutical for the detection of metastases of malignant melanoma.

Topics: Antibodies, Neoplasm; Female; Glutathione; Humans; Isotope Labeling; Male; Melanoma; Middle Aged; Radioimmunodetection; Reagent Kits, Diagnostic; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Technetium

In order to avoid complications after regional chemotherapy (isolated hyperthermic perfusion) of the extremities, rapid measurement of blood leakage from the extracorporeal to the systemic circulation is important. A method using technetium-99m in vivo red blood cell (RBC) labelling is reported that provides results within 3 min. Blood samples drawn from the systemic and the extracorporeal circulation were measured for 99mTc activity using a mobile well counter, and the leakage values calculated. The mean result was 7.6% +/- 6.5%/15 min (n = 209). The corresponding flow rate was 100.2 +/- 85.7 ml/15 min (mean +/- SD). The values for isolation perfusion of the upper and the lower extremities are compared. The leakage results using 99mTc RBC labelling were correlated with other blood pool markers. Iodine-125 human serum albumin and indium-113 m transferrin were administered in subgroups of 4 and 19 patients simultaneously. Using linear regression, the coefficient of correlation was 0.72 for 99mTc/113mIn and 0.58 for 99mTc/125I. Comparison with the alternatives suggests that the rapid method of leakage measurement after 99mTc RBC labelling can be considered one of the most practicable and reliable methods available.

Topics: Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Erythrocytes; Extremities; Female; Humans; Male; Melanoma; Melphalan; Middle Aged; Radionuclide Imaging; Skin Neoplasms; Sodium Pertechnetate Tc 99m; Time Factors

In 71 patients with malignant melanoma 85 radioimmunoscintigraphies (RIS) with 99mTc-radiolabeled F(ab')2 fragments of a murine monoclonal antibody have been performed. The antibody is specific for an epitope of the HMW-MAA glycoprotein complex which is present in 90% of melanoma tissue samples. Sensitivity for RIS was 79% (73 metastatic sites out of a total of 92). 20 previously unknown lesions were found and there were also 2 false positives. Conventional staging procedures alone revealed 78% of the metastatic sites (72 of 92). No side effects were observed. RIS was especially useful for detection of lymph node metastases not found by conventional methods and is therefore considered complementary to conventional preoperative staging procedures.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Female; Humans; Immunoglobulin Fab Fragments; Lymphatic Metastasis; Male; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Radionuclide Imaging; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Lymphoscintigraphy; Male; Melanoma; Middle Aged; Skin Neoplasms; Sodium Pertechnetate Tc 99m

The possibility of using radiolabelled monoclonal antibody fragments to image uveal melanomas has been assessed in a pilot study. 99mTc labelled F(ab')2 fragments of MoAb 225.28S raised against cutaneous melanomas were used. Initially 10 patients were imaged. In five patients the clinical findings were typical of uveal melanoma. Immunoscintigraphy was positive in all five cases. In a further five patients there was doubt about the diagnosis. One was though to have a choroidal haemangioma but failed to respond to treatment and immunoscintigraphy was positive, suggesting a diagnosis of melanoma. Two patients were assigned a diagnosis of choroidal haemangioma, one of melanocytoma or possible retinal pigment epithelium carcinoma, and one of metastasis. Immunoscintigraphy was negative in all these four cases. In combination with established diagnostic tests immunoscintigraphy may have a part to play in differentiating uveal melanoma from other similar tumours.

Topics: Adult; Aged; Antibodies, Monoclonal; Choroid Neoplasms; Diagnosis, Differential; Female; Hemangioma; Humans; Immunoglobulin Fab Fragments; Male; Melanoma; Middle Aged; Radionuclide Imaging; Skin Neoplasms; Sodium Pertechnetate Tc 99m; Uveal Neoplasms

Organ distribution and blood concentration profiles were compared following injection of mice with radiolabeled test agents via the lateral tail vein or retroorbital venous sinus. Monoclonal antibodies directed against B16 melanoma of C57BL/6 origin were labeled with iodine-125. Thymocytes from BALB/c mice and B16 melanoma cells were labeled with technetium-99m sodium pertechnetate (Na 99mTcO4). Animals were injected with 5 microCI of iodinated antibody, 5 X 10(5) syngeneic thymocytes, 2.5 X 10(5) melanoma cells, or 10 microCi Na 99mTcO4 in 0.2 ml saline via either route. In non-tumor-bearing C57BL/6 mice radiolabeled monoclonal antibody was found primarily in the gastrointestinal tract, liver, and blood. Na 99mTcO4 localized in the gastrointestinal tract, 99mTc-labeled thymocytes in the spleen and liver, and 99mTc-labeled B16 melanoma cells in the liver and lungs. Pharmacokinetic analysis of blood samples taken 4, 8, and 12 min following injection of the labeled agents suggested that the iodinated antibody had less vascular permeability than Na 99mTcO4 and that thymocytes and B16 melanoma cells were trapped in the pulmonary vasculature as they passed through the lungs. It is noteworthy that no biologically significant differences in organ distribution patterns or blood decay profiles were found between lateral tail vein and retroorbital routes. The data clearly indicate that these routes can be used interchangeably with one another for intravenous injections.

Topics: Animals; Antibodies, Monoclonal; Capillary Permeability; Injections, Intravenous; Iodine Radioisotopes; Kinetics; Melanoma; Mice; Mice, Inbred BALB C; Orbit; Rats; Sodium Pertechnetate Tc 99m; Tail; Thymus Gland; Tissue Distribution

A non-invasive method of detecting intraocular mass lesions is described which uses 67gallium citrate and 99m-technetium pertechnetate. It was used in 33 cases. In 73.7% of the patients with malignant melanoma of the eye there was a significant increase in the storage of the tracer. There was no difference in the results obtained with 67gallium citrate and 99m-technetium pertechnetate. Small, flat and peripheral tumors may not be detected. In some cases old intraocular hemorrhages may also lead to false-positive results. In contrast to the 32P-test the method described can be used in cases with opaque media. The radiation dose is about one-tenth of that given with the 32P-test.

Topics: Adolescent; Adult; Aged; Choroid Neoplasms; Diagnosis, Differential; Eye Neoplasms; Female; Gallium Radioisotopes; Humans; Iris Diseases; Male; Melanoma; Middle Aged; Nevus; Radionuclide Imaging; Sarcoma; Sodium Pertechnetate Tc 99m; Technetium; Uveal Neoplasms