Synthesis of a carbon-11 labeled nonsteroidal antiandrogen as a potential radioligand for pet imaging of prostate cancer

Autor: Phillip S. Sherman, Kyle Kuszpit, Douglas M. Jewett, M. E. Van Dort, Y. W. Jung
Rok vydání: 2001
Předmět:
Zdroj: Journal of Labelled Compounds and Radiopharmaceuticals. 44:S330-S332
ISSN: 0362-4803
DOI: 10.1002/jlcr.25804401116
Popis: The hormone dependency of prostate cancer is well established and androgen receptor (AR) expression is frequently observed in primary prostate tumors and metastases (1). As a consequence, the development of radioligands that target the AR for prostate tumor imaging is an active area of research (2). The majority of these studies to date have focused on steroid-based ligands, including the naturally occurring androgens (testosterone, dihydrotestosterone) and synthetic steroids (mibolerone, metribolone) (3,4). The recent emergence of AR-selective, high-affinity, nonsteroidal antiandrogens such as RU 59063, (Table l), offers a usehl alternative approach towards AR radioligand development (5). Our goal in this study was to develop a suitable carbon-1 1 labeled nonsteroidal AR radioligand for PET imaging of prostate cancer. We recently showed that replacement of the trifluoromethyl group of RU 59063 with iodine (DTIB, Table 1) leads to a 3-fold enhancement in AR binding affinity (6). This observation led us to synthesize the N-methylated hydantoin and thiohydantoin derivatives (laJb), which were subsequently shown to retain high affinity towards AR (Table 1). Since the synthesis of ["C]lJ by direct N-["C]methylation of its normethyl precursor is not feasible (due to preferential methylation on sulfur), the N-methyl derivative was selected for carbon-1 1 labeling. We report here the radiosynthesis of [ " C ] b for evaluation as a AR radioligand for PET.
Databáze: OpenAIRE
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