RT Journal Article SR Electronic T1 THE IN VIVO AND IN VITRO METABOLIC PROFILE OF 99MTC-NC100668, A NEW TRACER FOR IMAGING VENOUS THROMBOEMBOLISM: IDENTIFICATION AND BIODISTRIBUTION OF THE PRINCIPAL RADIOLABELED METABOLITE JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1128 OP 1135 DO 10.1124/dmd.106.009696 VO 34 IS 7 A1 Edwards, David A1 Battle, Mark A1 Lear, Rochelle A1 Farrar, Gill A1 Barnett, D. Jon A1 Godden, Vanessa A1 Coombes, Catherine A1 Oliveira, Alexandra A1 Ahlström, Håkan YR 2006 UL http://dmd.aspetjournals.org/content/34/7/1128.abstract AB 99mTc-NC100668 [Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-Tyr(3-iodo)-Thr-Leu-Leu-Lys-Gly-NC100194] is a radiopharmaceutical imaging agent being developed to aid the diagnosis of thromboembolism. The stability profile of 99mTc-NC100668 was investigated by high-performance liquid chromatography (HPLC) after in vitro exposure to blood and plasma obtained from rat and human, as well as to urine and bile obtained from rat. The metabolic profile of 99mTc-NC100668 exposed to human and rat hepatic S9 (a liver homogenate-rich cytochrome P450) was also studied. The profile of 99mTc-labeled species in plasma, urine, and bile was investigated following i.v. administration of 99mTc-NC100668 to rat. The major species observed in vitro and in vivo consisted of the 99mTc-chelator (NC100194) [N,N-Bis(N-(1,1-dimethyl-2-(hydroxylimino-)propyl)aminoethyl)aminoethylamine] attached to the C-terminal amino acid residue and referred to as 99mTc-complex of Gly-NC100194. The identity of the major metabolite was confirmed by cochromatography with an authentic standard and the genuine metabolite using a second HPLC method. The minor metabolites were sodium pertechnetate (99mTc) and 99mTc-NC100194. In addition, a small number of other species were transiently observed in vitro; they were not investigated further. The biodistribution of the major metabolite was studied in male Wistar rats. The affinity of the major metabolite toward plasma clot was established using a plasma clot-forming assay. A minor uptake of 99mTc-complex of Gly-NC100194 in the plasma clot and a rapid removal from the body were noted. In conclusion, the metabolites of 99mTc-NC100668 are not anticipated to have a negative impact on the ability of the test substance to image blood clots. The American Society for Pharmacology and Experimental Therapeutics