RT Journal Article SR Electronic T1 NC100668, a New Tracer Tested for Imaging of Venous Thromboembolism: Pharmacokinetics and Metabolism in Humans JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1979 OP 1984 DO 10.1124/dmd.106.014126 VO 35 IS 11 A1 Kim G. Toft A1 Judith A. Johnson A1 Inger Oulie A1 Tore Skotland YR 2007 UL http://dmd.aspetjournals.org/content/35/11/1979.abstract AB The 99mTc-complex of NC100668 [Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-Tyr(3-iodo)-Thr-Leu-Leu-Lys-Gly-NC100194] is a new tracer tested for nuclear medical imaging of venous thromboembolism. NC100668 is a 13-amino acid peptide with a Tc-binding chelator [NC100194; -NH-CH2-CH2-N(CH2-CH2-NH-C(CH3)2-C(CH3)=N-OH)2] linked to the C-terminal end. The present study was performed following injection of 99mTc-NC100668 in healthy human volunteers with five dose levels of NC100668 (20-2000 μg) and a constant radioactivity dose. The rate at which the radioactivity was cleared from blood was independent of gender and dose of NC100668; more than half of the 82% urinary clearance of radioactivity was obtained 2 h postinjection. The radioactivity in blood was reduced to 50% of initial values within 12 min; this was followed by a more gradual decrease with a half-life of 1.2 h and a terminal elimination half-life of 10.5 h. The plasma concentration of NC100668 decreased rapidly with an initial half-life of 5 to 10 min. The half-life after this initial phase could be estimated for only two of the subjects in the highest-dose group because the NC100668 concentration in the other samples at these time points was below the limit of detection of the liquid chromatography/mass spectrometry (LC/MS) method. LC/MS analyses of urine samples revealed the identity of two metabolites generated from the C-terminal end of the molecule; Gly-NC100194 was identified as the major metabolite and NC100194 as a minor metabolite. The estimated sum of these two metabolites is in the same magnitude as the recoveries of 99mTc in these samples, indicating that most of the 99mTc excreted in urine is bound to one of these metabolites. The American Society for Pharmacology and Experimental Therapeutics