Title: New Transient Receptor Potential Vanilloid Subfamily Member 1 Positron Emission Tomography Radioligands: Synthesis, Radiolabeling, and Preclinical Evaluation
Authors: van Veghel, Daisy ×
Cleynhens, Jan
Pearce, Larry V
Deandrea-Lazarus, Ian A
Blumberg, Peter M
Van Laere, Koen
Verbruggen, Alfons
Bormans, Guy #
Issue Date: Apr-2013
Series Title: ACS Chemical Neuroscience vol:4 issue:4 pages:624-34
Abstract: The transient receptor potential vanilloid subfamily member 1 (TRPV1) cation channel is known to be involved in pain nociception and neurogenic inflammation, and accumulating evidence suggests that it plays an important role in several central nervous system (CNS)-related disorders. TRPV1-specific positron emission tomography (PET) radioligands can serve as powerful tools in TRPV1-related (pre)clinical research and drug design. We have synthesized several potent TRPV1 antagonists and accompanying precursors for radiolabeling with carbon-11 or fluorine-18. The cinnamic acid derivative [(11)C]DVV24 and the aminoquinazoline [(18)F]DVV54 were successfully synthesized, and their biological behavior was studied. In addition, the in vivo behavior of a (123)I-labeled analogue of iodo-resiniferatoxin (I-RTX), a well-known TRPV1 antagonist, was evaluated. The binding affinities of DVV24 and DVV54 for human TRPV1 were 163 ± 28 and 171 ± 48 nM, respectively. [(11)C]DVV24, but not [(18)F]DVV54 or (123)I-RTX, showed retention in the trigeminal nerve, known to abundantly express TRPV1. Nevertheless, it appears that ligands with higher binding affinities will be required to allow in vivo imaging of TRPV1 via PET.
ISSN: 1948-7193
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Radiopharmaceutical Research
Nuclear Medicine & Molecular Imaging
× corresponding author
# (joint) last author

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