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 |
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| Rok vydání: | 2001 |
| Předmět: |
Chemistry
Metribolone medicine.medical_treatment Organic Chemistry Radiosynthesis medicine.disease Biochemistry Analytical Chemistry Androgen receptor Prostate cancer chemistry.chemical_compound medicine.anatomical_structure Prostate Dihydrotestosterone Drug Discovery medicine Radioligand Cancer research Mibolerone Radiology Nuclear Medicine and imaging Spectroscopy medicine.drug |
| Zdroj: | Journal of Labelled Compounds and Radiopharmaceuticals. 44:S330-S332 |
| ISSN: | 0362-4803 |
| 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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