کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1393374 | 1501208 | 2008 | 9 صفحه PDF | دانلود رایگان |
The estrogen receptors (ERs) are attractive targets in the treatment of breast cancer and the development of receptor-based breast cancer imaging agents for diagnostic use in biomedical imaging technique positron emission tomography (PET). Tetrahydroisoquinoline derivatives are a class of selective estrogen receptor modulators (SERMs) with high binding affinity and specificity exhibiting up to 50 folds for ERα over ERβ. New carbon-11 labeled tetrahydroisoquinoline derivatives, [11C]methyl 1-(2-(4-(2-(4-fluorophenyl)-6-hydroxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenoxy)ethyl)piperidine-4-carboxylate ([11C]10a) and [11C]methyl 1-(2-(4-(2-(4-chlorophenyl)-6-hydroxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenoxy)ethyl)piperidine-4-carboxylate ([11C]10b), have been first designed, synthesized and evaluated. The target tracers were prepared by O-[11C]methylation of their corresponding precursors using [11C]CH3OTf and isolated by solid-phase extraction (SPE) purification procedure in 40–60% radiochemical yields, which were decay corrected to the end of bombardment (EOB), based on [11C]CO2. The overall synthesis time was 15–20 min from EOB. The radiochemical purity was >99%, and specific activity was in a range of 74–111 GBq/μmol at the end of synthesis (EOS). Preliminary findings from in vitro biological assay indicate that the synthesized derivatives displayed similar potencies in the MCF-7 human breast cancer cell line in comparison with 4-hydroxytamoxifen, a well-known potent SERM. These results encourage further in vivo evaluation of carbon-11 labeled tetrahydroisoquinoline derivatives as new potential SERM radioligands for PET imaging of ER expression in breast cancer.
This paper reports the synthesis and preliminary biological evaluation of new carbon-11 labeled tetrahydroisoquinoline derivatives, potential SERM radioligands for PET imaging of ER expression in breast cancer.Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 43, Issue 10, October 2008, Pages 2211–2219