sodium-pertechnetate-tc-99m and Glioblastoma

The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET alpha-emitter astatine-211 ((211)At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 ((123)I), 340-fold for technetium-99m pertechnetate ((99m)TcO(4)(-)) and 60-fold for (211)At. Cellular (211)At accumulation was found to be dependent on extracellular Na(+) ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and (99m)TcO(4)(-) uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated (211)At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and (211)At were rapidly (apparent t(1/2) 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times ((123)I), 25 times ((99m)TcO(4)(-)) and 10 times ((211)At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of (123)I and (211)At, respectively, was found in NIS tumours by region of interest analysis ( n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for (123)I, 5.2 h for (211)At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBq(tumour) for (131)I and 50.3 Gy/MBq(tumour) for (211)At). In conclusion, NIS-expressing tumour cell lines of different origin displayed specific radionuclide uptake in vitro and in vivo. We provide first direct evidence that the high-energy alpha-emitter (211)At is efficiently transported by NIS. Application of (211)At may direct higher radiation doses to experimental tumours than those calculated for (131)I. Thus, (211)At may represent a promising alternative radionuclide for future NIS-based tumour thera

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Animals; Astatine; Biomarkers, Tumor; Colonic Neoplasms; Gene Expression; Glioblastoma; Humans; Iodine Radioisotopes; Mice; Mice, Nude; Neoplasm Transplantation; Radionuclide Imaging; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Symporters; Thyroid Neoplasms; Tissue Distribution; Tumor Cells, Cultured

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

(99m)Tc-Sestamibi (MIBI) has been successfully applied in recurrent glioblastoma. The aim of this study was to evaluate the incremental diagnostic information of MIBI as a tumor-avid radiopharmaceutical compared with (99m)Tc-pertechnetate ((99m)Tc) as sole indicator of the integrity of the blood-brain barrier. Twenty-five patients with confirmed recurrent brain tumors were included. MIBI SPET was performed 10 min after injection of 555 MBq MIBI intravenously with a triple-headed gamma camera equipped with LE-UHR-PAR collimators over 360 degrees (3 degrees /step) and stored in a 128(2) matrix. Identical acquisition parameters were used for (99m)Tc SPET, which was acquired 3 h after injection of 740 MBq (99m)Tc. Normalized tumor uptake (NU) was calculated from attenuation-corrected transaxial slices. In addition, tumor/plexus, tumor/nasopharynx, and tumor/parotid gland ratios were assessed in both studies. No statistically significant differences were detected for the mean NU of tumor tissue with MIBI (0.26 +/- 0.10) and (99m)Tc (0.39 +/- 0. 33) and for the tumor/nasopharynx and tumor/parotid gland ratios; only the tumor/plexus ratio was significantly higher for (99m)Tc than for MIBI (p < 0.05). In conclusion, our data indicate that MIBI scintigraphy in brain tumors at 10 min postinjection reveals no additional visual information over that provided by the conventional (99m)Tc-pertechnetate brain scan, and in addition, tracer retention reflects primarily blood-brain barrier damage.

Topics: Adult; Blood-Brain Barrier; Brain Neoplasms; Female; Glioblastoma; Humans; Male; Middle Aged; Oligodendroglioma; Radionuclide Imaging; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Sestamibi

The intensity of parenchymal brain lesions was compared using Tc-99m pertechnetate and Tc-99m phosphate. The following conclusions were made: 1. If the Tc-99m phosphate intensity is greater than the intensity of the Tc-99m pertechnetate scan, and the patient is evaluated within four weeks of ictus, the lesion is a CVA (P less than .001). 2. If the Tc-99m phosphate intensity is less than or equal to the intensity of the Tc-99m pertechnetate scan, and the patient is evaluated within four weeks of ictus, the parenchymal lesion is not a CVA (P less than .001). 3. If the evaluation takes place longer than six weeks after ictus, then no evaluation about the nature of the lesion can be made based upon uptake of Tc-99m phosphate and Tc-99m pertechnetate.

Topics: Adult; Brain Neoplasms; Diphosphonates; Glioblastoma; Glioma; Humans; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Tc 99m Medronate; Tomography, X-Ray Computed

Topics: Brain; Brain Abscess; Brain Diseases; Brain Neoplasms; Cerebrovascular Disorders; Glioblastoma; Humans; Meningioma; Organotechnetium Compounds; Pentetic Acid; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Sugar Acids; Technetium; Tomography, X-Ray Computed; Wounds and Injuries