title: 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: Diatide Research Laboratories, 9 Delta Drive, Londonderry, New Hampshire 03053, USA. john.cyr@bayer.com
authors: John E
authors: JE
authors: Cyr
authors: Daniel A
authors: DA
authors: Pearson
authors: Carol A
authors: CA
authors: Nelson
authors: Barbara A
authors: BA
authors: Lyons
authors: Yongyong
authors: Y
authors: Zheng
authors: Judit
authors: J
authors: Bartis
authors: Jiafang
authors: J
authors: He
authors: Melchor V
authors: MV
authors: Cantorias
authors: Robertha C
authors: RC
authors: Howell
authors: Lynn C
authors: LC
authors: Francesconi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D005260:Female; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D013004:Somatostatin; C444119:technetium Tc 99m depreotide
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