Isolation, characterization, and biological evaluation of syn and anti diastereomers of [(99m)Tc]technetium depreotide: a somatostatin receptor binding tumor imaging agent.

Abstract	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.
Authors	John E Cyr, Daniel A Pearson, Carol A Nelson, Barbara A Lyons, Yongyong Zheng, Judit Bartis, Jiafang He, Melchor V Cantorias, Robertha C Howell, Lynn C Francesconi
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 18 Pg. 4295-303 (Sep 06 2007) ISSN: 0022-2623 [Print] United States
PMID	17691760 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	Organotechnetium Compounds Radiopharmaceuticals Receptors, Somatostatin Somatostatin technetium Tc 99m depreotide
Topics	Animals Cell Line, Tumor Circular Dichroism Female Isotope Labeling Magnetic Resonance Spectroscopy Mice Mice, Nude Neoplasm Transplantation Neoplasms (diagnostic imaging, metabolism) Organotechnetium Compounds (chemistry, isolation & purification, pharmacokinetics) Pancreatic Neoplasms Radioligand Assay Radionuclide Imaging Radiopharmaceuticals (chemistry, isolation & purification, pharmacokinetics) Rats Receptors, Somatostatin (metabolism) Somatostatin (analogs & derivatives, chemistry, isolation & purification, pharmacokinetics) Stereoisomerism Tissue Distribution

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