technetium-tc-99m-depreotide and Neoplasms

There has been an exponential growth in the development of radiolabeled peptides for diagnostic and therapeutic applications in oncology. Peptides have fast clearance, rapid tissue penetration, low antigenicity and can be produced easily and inexpensively. However, peptides have problems with in vivo catabolism, unwanted physiological effects, and chelate attachment. The approved 111In-DTPA-OctreoScan, a somatostatin receptor binder, is well established for diagnosis of neuroendocrine tumors. NeoTect, an approved, 99mTc-labeled, somatostatin-receptor-binding analogue has good specificity for lung cancer detection. The receptors for Vasoactive Intestinal Peptide, Cholecystokinin-B/gastrin, Bombesin, Epidermal Growth Factor, and Alpha Melanocyte Stimulating Hormone and the Integrin, alpha(v)beta(3), are under active investigation as targets. Octreotide and its analogues labeled with 111In, 90Y, 64Cu or 177Lu are under study for the treatment of patients with promising results.

Topics: Humans; Intercellular Signaling Peptides and Proteins; Neoplasms; Octreotide; Pentetic Acid; Peptides; Peptides, Cyclic; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Peptide; Somatostatin

The early and later eluting [(99m)TcO]depreotide products on RP-HPLC were confirmed to be the anti and syn diastereomers, respectively, based on proton NMR and circular dichroism spectroscopy. NMR provided evidence of a folded, conformationally constrained structure for the syn diastereomer. The syn diastereomer is predominant (anti/syn approximately 10:90) in the [(99m)TcO]depreotide preparation and shows a slightly higher affinity (IC50 = 0.15 nM) for the somatostatin receptor than the anti diastereomer (IC50 = 0.89 nM). Both diastereomers showed higher binding affinities than the free peptide (IC(50) = 7.4 nM). Biodistribution studies in AR42J tumor xenograft nude mice also showed higher tumor uptake for syn [(99m)TcO]depreotide (6.58% ID/g) than for the anti [(99m)TcO]depreotide (3.38% ID/g). Despite the differences in biological efficacy, the favorable binding affinity, tumor uptake, and tumor-to-background ratio results for both diastereomeric species predict that both are effective for imaging somatostatin receptor-positive tumors in vivo.

Topics: Animals; Cell Line, Tumor; Circular Dichroism; Female; Isotope Labeling; Magnetic Resonance Spectroscopy; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms; Organotechnetium Compounds; Pancreatic Neoplasms; Radioligand Assay; Radionuclide Imaging; Radiopharmaceuticals; Rats; Receptors, Somatostatin; Somatostatin; Stereoisomerism; Tissue Distribution