Rijks L J, van den Bos J C, van Doremalen P A, Boer G J, de Bruin K, Janssen A G, van Royen E A
Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Nucl Med Biol. 1998 Nov;25(8):791-8. doi: 10.1016/s0969-8051(98)00042-0.
On the basis of the observed high selective binding to both the human and rat progesterone receptor (PR) in vitro, three 17alpha-iodovinyl-substituted nortestosterone derivatives, i.e., the Z-isomer of 17alpha-iodovinyl-19-nortestosterone (Z-IVNT; Z-IPG1) and both the stereoisomers of 17alpha-iodovinyl-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 uptake in the uterus and ovaries could only be demonstrated for Z-[123I]IPG2. The target tissue uptake selectivity was, however, low, with the highest uterus-to-nontarget tissue uptake ratios observed at 2-4 h postinjection (p.i.), being 4.4, 1.8, and 7.4 for the uterus-to-blood, -fat, and -muscle ratio, respectively. For Z-[123I]IPG2, distribution was also studied in dimethylbenzanthracene (DMBA)-induced mammary tumour-bearing rats and in normal rabbits. Mammary tumour uptake of Z-[123I]IPG2 in the mammary tumour-bearing rat was also found to be PR-specific. In rabbits, higher selective target tissue uptake of Z-[123I]IPG2 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 conclusion, Z-[123I]IPG2, which displayed high binding affinity for both the human and rat PR in vitro, showed specific PR-mediated target tissue 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-[123I]IPG2 can be of potential use as PR imaging agent in breast cancer.
基于在体外观察到的对人和大鼠孕酮受体（PR）的高选择性结合，选择了三种17α-碘乙烯基取代的诺睾酮衍生物，即17α-碘乙烯基-19-诺睾酮的Z-异构体（Z-IVNT；Z-IPG1）以及17α-碘乙烯基-18-甲基-11-亚甲基-19-诺睾酮的两种立体异构体（E-和Z-IPG2）进行放射性碘化，随后评估其作为人乳腺癌PR成像潜在放射性配体的性能。在雌性大鼠中研究了它们在靶组织中的摄取、滞留和摄取选择性。分布研究表明，仅Z-[123I]IPG2能显示出PR介导的子宫和卵巢摄取。然而，靶组织摄取选择性较低，注射后2 - 4小时观察到的子宫与非靶组织摄取比最高，子宫与血液、脂肪和肌肉的摄取比分别为4.4、1.8和7.4。对于Z-[123I]IPG2，还在二甲基苯并蒽（DMBA）诱导的荷乳腺肿瘤大鼠和正常兔中进行了分布研究。在荷乳腺肿瘤大鼠中，Z-[123I]IPG2在乳腺肿瘤中的摄取也被发现是PR特异性的。在兔中，观察到Z-[123I]IPG2的靶组织摄取选择性高于大鼠，注射后2 - 4小时子宫与血液、脂肪和肌肉的摄取比分别为6.6、2.2和21.3。总之，Z-[123I]IPG2在体外对人和大鼠PR均显示出高结合亲和力，在体内大鼠和兔中显示出PR介导的特异性靶组织摄取，在兔中摄取选择性最高。由于结合特性在不同物种间似乎有所不同，可能需要在乳腺癌患者中进行一项初步研究，以确定Z-[123I]IPG2是否有可能作为乳腺癌PR成像剂。
