Open AccessDevelopment of [123I]IPEB and [123I]IMPEB as SPECT Radioligands for Metabotropic Glutamate Receptor Subtype 5
Author(s) -
Kun-Eek Kil,
Aijun Zhu,
Zhaoda Zhang,
JiKyung Choi,
Sreekanth Kura,
Chunyu Gong,
AnnaLiisa Brownell
Publication year - 2014
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml500007z
Subject(s) - nuclear medicine , positron emission tomography , single photon emission computed tomography , brain positron emission tomography , spect imaging , striatum , emission computed tomography , glutamate receptor , medicine , neuroimaging , chemistry , neuroscience , preclinical imaging , receptor , in vivo , psychology , biology , microbiology and biotechnology , dopamine
mGlu5 play an important role in physiology and pathology to various central nervous system (CNS) diseases. Several positron emission tomography (PET) radiotracers have been developed to explore the role of mGlu5 in brain disorders. However, there are no single photon emission computed tomography (SPECT) radioligands for mGlu5. Here we report development of [(123)I]IPEB ([(123)I]1) and [(123)I]IMPEB ([(123)I]2) as mGlu5 radioligands for SPECT. [(123)I]1 and [(123)I]2 were produced by copper(I) mediated aromatic halide displacement reactions. The SPECT imaging using mouse models demonstrated that [(123)I]1 readily entered the brain and accumulated specifically in mGlu5-rich regions of the brain such as striatum and hippocampus. However, in comparison to the corresponding PET tracer [(18)F]FPEB, [(123)I]1 showed faster washout from the brain. The binding ratios of the striatum and the hippocampus compared to the cerebellum for [(123)I]1 and [(18)F]FPEB were similar despite unfavorable pharmacokinetics of [(123)I]1. Further structural optimization of 1 may lead to more viable SPECT radiotracers for the imaging of mGlu5.