Isolation, characterization, and biological evaluation of Syn and Anti diastereomers of [99mTc]Technetium depreotide:: a somatostatin receptor binding tumor Imaging agent

The early and later eluting [(TcO)-Tc-99m]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 similar to 10:90) in the [(TcO)-Tc-99m]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 (IC50 = 7.4 nM). Biodistribution studies in AR42J tumor xenograft nude mice also showed higher tumor uptake for syn [(TcO)-Tc-99m]depreotide (6.58% ID/g) than for the anti [(TcO)-Tc-99m]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 diastereometic species predict that both are effective for imaging somatostatin receptor-positive tumors in vivo.