nc100692 and arginyl-glycyl-aspartic-acid

The (99m)Tc complex of NC100692 is being evaluated as a diagnostic agent for the detection of angiogenesis. In the present study, human urine samples from a clinical Phase I study were analysed using reversed-phase liquid chromatography coupled with an ion-trap mass spectrometer (LC-MS) in order to estimate the amount of intact NC100692 and any metabolites excreted in urine following intravenous injection of 150microg (99m)Tc-NC100692. Only intact NC100692 was observed in these urine samples, no metabolites were detected, in contrast to data earlier reported for rat urine where two metabolites and no NC100692 were observed. Within 4-8h after injection, 30+/-6% of the injected NC100692 was excreted in the urine, with the majority (23+/-5%) recovered within the first hour post-injection. There was good agreement between the calculated urinary recoveries of NC100692 and total radioactivity in urine samples voided approximately 1h post-injection. NC100692 constituting 98+/-24% of the total urinary (99m)Tc recovery indicating that the (99m)Tc excreted during this period was most likely excreted as (99m)Tc-NC100692. The ratio of NC100692 to (99m)Tc decreased in the urine samples as a function of time following injection for all subjects; this change is most likely due to reduced accuracy in the results at low levels of NC100692.

Topics: Adult; Chromatography, High Pressure Liquid; Female; Freeze Drying; Humans; Male; Mass Spectrometry; Neovascularization, Pathologic; Oligopeptides; Peptides, Cyclic; Radiography; Radiopharmaceuticals; Single-Blind Method; Technetium

The 99mTc complex of NC100692 is being evaluated as a diagnostic agent for imaging of angiogenesis. We here report in vivo studies performed with NC100692 and 14C-labelled NC100692 using liquid chromatography coupled to either an ion-trap mass spectrometer or a radiochemical detector. Following injection of 14C-labelled NC100692, only the parent compound and no metabolites was observed in rat blood, whereas no parent compound and only 1 metabolite was observed in urine. Analysis of rat urine samples with liquid chromatography with mass spectrometric detection following administration of NC100692 verified the absence of the parent compound and showed the presence of 2 metabolites. The structures of the 2 metabolites were identified based on mass spectra and accurate mass determinations. The major metabolite was identified as the molecule obtained following hydrolytic cleavage at the end of the C-terminal amino acid of NC100692. The minor metabolite was identified as that obtained following removal of phenylalanine within the cyclic structure of the major metabolite.

Topics: Animals; Autoradiography; Carbon Radioisotopes; Male; Neovascularization, Pathologic; Oligopeptides; Peptides, Cyclic; Rats; Rats, Sprague-Dawley