Preclinical evaluation of a positron emitting progestin ([¹⁸F]fluoro-16α-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography

Three 21-fluoro-progestins were investigated as potential imaging agents for the in vivo assessment of human progesterone receptor positive neoplasms with positron emission tomography. In competitive binding assays these compounds demonstrated high specificity, competing only for progesterone receptors. Binding to other steroid receptor types was negligible. Based on its high affinity binding, 21-fluoro-16α-methyl-19-norprogesterone was selected for further evaluation in vivo. Tissue distribution studies in immature estrogen primed female rats revealed high uterine uptake of 21-[¹⁸F]fluoro-16α-methyl-19-norprogesterone ([¹⁸F]FMNP). At 60 min after injection the ratio of uptake of radioactivity by uterine tissue to that of blood was 7. This ratio increased to 24 at 180 min. A selective decrease in uterine uptake was observed after administration of [¹⁸F]FMNP with excess unlabelled progestin. Rats bearing hormone responsive MT-W9A mammary adenocarcinomas were used to examine [¹⁸F]FMNP for tumour uptake. Animals were used irrespective of the phase of the estrous cycle. At 180 min the uterus to blood ratio and the tumour to blood ratio ranged from 3 to 20 and 3 to 17, respectively. Uterine and tumour tissue was assayed for cytosolic estrogen and progesterone receptors using a dextran-coated charcoal method and Scatchard plot analysis. The results indicate that the in vivo uptake of [¹⁸F]FMNP by uterine and mammary tumour tissue correlated well with the progesterone receptor concentration (r_s = 0.98 and r_s = 0.88, respectively). It is concluded that the uptake of [¹⁸F]FMNP by progesterone receptor positive tissue in vivo is primarily receptor related and that this uptake is attributable to the progesterone receptor. The study demonstrates the potential applicability of [¹⁸F]FMNP and positron emission tomography for imaging progesterone receptor positive neoplasms.