Assessment of
estrogen receptors and
progesterone receptors (PR) with PET may allow the determination of the
hormone responsiveness of
tumors without the need for multiple biopsies, and the monitoring of the effect of hormonal
therapy. In spite of the favourable characteristics of 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone ([18F]
FENP) found in preclinical studies, the compound failed to reveal the presence of PR in
breast carcinomas and
meningiomas. In view of the clinical significance of the PR assay in human
breast cancer, it is worthwhile to explore mechanisms that are potentially involved in the inadequacy of [18F]
FENP to image PR with PET. Our present study on the in vivo metabolism of [18F]
FENP in humans demonstrates a rapid clearance and biotransformation of the compound. Results of incubation experiments suggest that the metabolic conversion of [18F]
FENP is not restricted to the liver, but also occurs in blood cells (presumably the erythrocytes) and
tumors (breast carcinomas and
meningiomas). The predominant metabolite of [18F]
FENP in plasma during the rapid distribution phase and in
tumors is identified as 20-dihydro-[18F]
FENP. The conversion of [18F]
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 [18F]
FENP, or its significance in the ineffectiveness of [18F]
FENP as an imaging agent for PR. On the other hand, the ability of
breast carcinomas and
meningiomas to metabolize [18F]
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 [18F]
fluorine labeled
progestin in an early stage of future screening procedures.