A new positron emission tomography imaging agent for the serotonin transporter: synthesis, pharmacological characterization, and kinetic analysis of [11C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine ([11C]AFM)

Nuclear Medicine and Biology
Yiyun HuangMarc Laruelle

Abstract

The synthesis, radiolabeling, and in vitro and in vivo evaluation of a new positron emission tomography (PET) radioligand for the serotonin transporter (SERT), [(11)C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine ([(11)C]AFM) is reported. AFM was prepared from 4-chloro-3-nitrobenzyl acetate and thiosalicylic acid in a five-step synthetic sequence. In binding studies in vitro with cloned human transporters, AFM displayed high binding affinity (Ki 1.04 nmol/L for hSERT) and good selectivity (Ki 664 nmol/L for hNET and >10,000 nmol/L for hDAT) for SERT. The radiolabled compound [(11)C]AFM was prepared in 30-37 minutes from its monomethylamine precursor by reaction with high specific activity [(11)C]iodomethane. Radiochemical yield was 12.3 +/- 8.1% based on [(11)C]iodomethane and specific activity was 1733 +/- 428 Ci/mmol at end of synthesis (EOS, n = 14). Radiochemical and chemical purity of the final product was >97%. Biodistribution studies in rats indicated that [(11)C]AFM entered the brain readily and localized in regions known to contain high concentrations of SERT, with high specific to nonspecific binding ratios. Furthermore, binding of [(11)C]AFM in SERT-rich regions was blocked by the cold compound AFM ...Continue Reading

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Citations

Oct 13, 2009·European Journal of Nuclear Medicine and Molecular Imaging·Ya-Yao HuangChyng-Yann Shiue
Dec 25, 2009·European Journal of Nuclear Medicine and Molecular Imaging·Kjell NågrenJuha O Rinne
Apr 3, 2009·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Ya-Yao HuangChyng-Yann Shiue
Aug 8, 2008·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Yunhang GuoBoli Liu
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Aug 8, 2012·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Ya-Yao HuangChyng-Yann Shiue
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Mar 17, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jean-Dominique GallezotYiyun Huang

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