NEW IODINATED PROGESTINS AS POTENTIAL LIGANDS FOR PROGESTERONE-RECEPTOR IMAGING IN BREAST-CANCER - PART 2 - IN-VIVO PHARMACOLOGICAL CHARACTERIZATION

On the basis of the observed high selective binding to both the human and rat progesterone receptor (PR) in vitro, three 17 alpha-iodovinyl- substituted nortestosterone derivatives, i.e., the Z-isomer of 17 alph a-iodovinyl-19-nortestosterone (Z-IVNT; Z-IPG1) and both the stereoiso mers of 17 odovinyl-18-methyl-11-methylene-19-nortestosterone (E and Z -IPG2), were selected for radio-iodination and subsequently evaluated as potential radioligands for PR imaging in human breast cancer. Their target tissue uptake, retention, and uptake selectivity were studied in female rats. The distribution studies revealed that PR-mediated upt ake in the uterus and ovaries could only be demonstrated for Z-[I-123] IPG2. The target tissue uptake selectivity was, however, low, with the highest uterus-to-nontarget tissue uptake ratios observed at 2-4 h po stinjection (p.i.), being 4.4, 1.8, and 7.4 for the uterus-to-blood, - fat, and -muscle ratio, respectively. For Z-[I-123]IPG2, distribution was also studied in dimethylbenzanthracene (DMBA)-induced mammary tumo ur-bearing rats and in normal rabbits. Mammary tumour uptake of Z-[I-1 23]IPG2 in the mammary tumour-bearing rat was also found to be PR spec ific. In rabbits, higher selective target tissue uptake of Z-[I-123]IP G2 was observed than in rats, resulting in uterus-to-blood, fat, and - muscle ratios of 6.6, 2.2, and 21.3 at 2-4 h p.i., respectively. In co nclusion, Z-[I-123]IPG2, which displayed high binding affinity for bot h the human and rat PR in vitro, showed specific PR-mediated target ti ssue uptake in rats and rabbits in vivo, the uptake selectivity being highest in the latter. Because the binding characteristics appeared to vary between species, a pilot study in breast cancer patients may be needed to decide whether Z-[I-123]IPG2 can be of potential use as PR i maging agent in breast cancer. NUCL MED BIOL 25;8:791-798, 1998. (C) 1 998 Elsevier Science Inc.