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

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.
AuthorsJohn 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
JournalJournal of medicinal chemistry (J Med Chem) Vol. 50 Issue 18 Pg. 4295-303 (Sep 6 2007) ISSN: 0022-2623 [Print] United States
PMID17691760 (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
  • Animals
  • Cell Line, Tumor
  • Circular Dichroism
  • Female
  • Isotope Labeling
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms (metabolism, radionuclide imaging)
  • Organotechnetium Compounds (chemistry, isolation & purification, pharmacokinetics)
  • Pancreatic Neoplasms
  • Radioligand Assay
  • Radiopharmaceuticals (chemistry, isolation & purification, pharmacokinetics)
  • Rats
  • Receptors, Somatostatin (metabolism)
  • Somatostatin (analogs & derivatives, chemistry, isolation & purification, pharmacokinetics)
  • Stereoisomerism
  • Tissue Distribution

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