METABOLISM OF A [F-18] FLUORINE LABELED PROGESTIN 21-[F-18]FLUORO-16-ALPHA-ETHYL-19-NORPROGESTERONE) IN HUMANS - A CLUE FOR FUTURE INVESTIGATIONS

Assessment of estrogen receptors and progesterone receptors (PR) with PET may allow the determination of the hormone responsiveness of tumor s without the need for multiple biopsies, and the monitoring of the ef fect of hormonal therapy. In spite of the favourable characteristics o f 21-[F-18]fluoro-16 alpha-ethyl-19-norprogesterone ([F-18]FENP) found in preclinical studies, the compound failed to reveal the presence of PR in breast carcinomas and meningiomas. In view of the clinical sign ificance of the PR assay in human breast cancer, it is worthwhile to e xplore mechanisms that are potentially involved in the inadequacy of [ F-18]FENP to image PR with PET. Our present study on the in vivo metab olism of[F-18]FENP in humans demonstrates a rapid clearance and biotra nsformation of the compound. Results of incubation experiments suggest that the metabolic conversion of [F-18]FENP is not restricted to the liver, but also occurs in blood cells (presumably the erythrocytes) an d tumors (breast carcinomas and meningiomas). The predominant metaboli te of [F-18]FENP in plasma during the rapid distribution phase and in tumors is identified as 20-dihydro-[F-18]FENP. The conversion of [F-18 ]FENP to its 20 alpha- or 20 beta-hydroxy metabolite has a deleterious effect on the binding affinity for PR. Our findings do not justify a conclusion as to the extent of in vivo extrahepatic biotransformation of [F-18]FENP, or its significance in the ineffectiveness of [F-18]FEN P as an imaging agent for PR. On the other hand, the ability of breast carcinomas and meningiomas to metabolize [F-18]FENP avidly appears to preclude selective imaging of PR in these tumors during the time of a PET examination. It is imperative to evaluate the metabolic stability of a [F-18]fluorine labeled progestin in an early stage of future scr eening procedures.