In vivo Recognition of Cyclopentadienyltricarbonylrhenium (CpTR) derivatives

In vivo metabolism of [Re-188]tricarbonyl(carboxycyclopentadienyl)rhenium ([Re-188]CpTR-CooH) and its glycine conjugate ([Re-188]CpTR-Gly) was investigated to estimate the applicability of cyclopentadienyltricarbonylrheniuili (CpTR) compounds to (186/188) Relabeling, reagents for poly. peptides and peptides. Both [Re-188]CpTR derivatives were stable after incubation in a buffered-solution and in murine plasma at 37degreesC for 6 h. Plasma protein binding was hardly observed with the two derivatives. However, different biodistribution and metabolic fates were observed with the two CpTR derivatives. While more lipophilic [Re-188]CpTR-COOH was excreted by both hepatobiliary and urinary excretion. the majority of less lipophilic [Re-188]CpTR-Gly was excreted by urinary excretion. In addition, while [Re-188]CpTR-Gly was rapidly excreted into urine as its intact structure, [Re-188]CpTR-COOH was metabolized to more hydrophilic compounds including its glycine conjugate, [Re-188]CpTR-Gly. Renal excretion of [Re-188]CpTR-Gly was significantly reduced in probenecid retreated mice. The present studies reinforced that CpTR core remained stable under biological environment. CpTR-COOH was partially recognized as an aromatic acid and was metabolized as such. However, glycine conjugation rendered CpTR-COOH hydrophilic enough to be excreted into urine without further metabolism. These findings Suggested that radiolabeling reagents that liberate [Re-186/188]CpTR-Gly from covalently conjugated (186/188) Re-labeled polypeptides and peptides by the action of renal brush border enzymes Would be useful to reduce renal radioactivity levels. (C)2003 Elsevier Science Inc. All rights reserved.