Synthesis and preliminary biological evaluation of new carbon-11 labeled tetrahydroisoquinoline derivatives as SERM radioligands for PET imaging of ER expression in breast cancer

Mingzhang Gao, Min Wang, Kathy D. Miller, George W. Sledge, Qi Huang Zheng

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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.

Original languageEnglish (US)
Pages (from-to)2211-2219
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Issue number10
StatePublished - Oct 1 2008



  • Cancer imaging
  • Carbon-11
  • Estrogen receptors
  • Positron emission tomography (PET)
  • Selective estrogen receptor modulators (SERMs)
  • Tetrahydroisoquinoline derivatives

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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