Preclinical evaluation of 4-[F-18]fluoroprolines: Diastereomeric effect onmetabolism and uptake in mice

The aim of this study was to evaluate the diastereomeric effect on uptake a nd metabolic behavior of (2S,4R)-4-[F-18]fluoro-L-proline (trans-[F-18]FPro ) and (2S,4S)-4-[F-18]fluoro-L-proline (cis-[F-18]FPro) in view of their po tential suitability as tracers for abnormal collagen synthesis. No-carrier- added 4-[F-18]fluoro-L-prolines were prepared according to the literature i n about 150 min (50-60% radiochemical yield). Both compounds exhibited high in vivo stability. The tumor uptake of cis-[F-18]FPro in osteosarcomas of mice was high and at 240 min postinjection reached 11.8 +/- 2.2 %ID/g compa red with 7.07 +/- 1.68 %ID/g for trans-[F-18]FPro, In contrat to trans-[F-1 8]FPro, which showed fast and complete renal clearance, the cis isomer was accumulated in the pancreas, and showed hepatic clearance and renal reuptak e. Speciation studies on tissue homogenates revealed protein incorporation only for cis-[F-18]FPro. However, due to the relatively slow protein incorp oration rate of cis-[F-18]FPro, the tumor uptake of both compounds in colon carcinomas, mammary carcinomas, and osteosarcomas 1 h postinjection predom inantly reflect amino acid transport. NUCL MED BIOL 26;3:259-265, 1999. (C) 1999 Elsevier Science Ins. All rights reserved.