title: Development of [(123)I]IPEB and [(123)I]IMPEB as SPECT Radioligands for Metabotropic Glutamate Receptor Subtype 5.
abstract: 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.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Kun-Eek
authors.initials: KE
authors.lastname: Kil
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Zhaoda
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Ji-Kyung
authors.initials: JK
authors.lastname: Choi
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Sreekanth
authors.initials: S
authors.lastname: Kura
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Gong
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Brownell
keywords: [123I]IMPEB; [123I]IPEB; in vivo imaging; metabotropic glutamate receptor subtype 5 (mGlu5); negative allosteric modulator (NAM); single photon emission computed tomography (SPECT)