2. Academic Validation
  3. Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/ β-Hydrolase Domain 6 (ABHD6)

Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/ β-Hydrolase Domain 6 (ABHD6)

  • J Med Chem. 2022 Dec 14. doi: 10.1021/acs.jmedchem.2c01485.
Karine Mardon,  Jayendra Z Patel 1,  Juha R Savinainen 2,  Damion H R Stimson,  Caitlin R M Oyagawa 3,  Natasha L Grimsey 3,  Mary-Anne Migotto,  Grace F M Njiru,  Brett R Hamilton 4,  Gary Cowin,  Jari Yli-Kauhaluoma 1,  Wim Vanduffel 5,  Idriss Blakey 6,  Rajiv Bhalla,  Christopher Cawthorne 7,  Sofie Celen 8,  Guy Bormans 8,  Kristofer J Thurecht 6,  Muneer Ahamed 6
Affiliations

Affiliations

  • 1 Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland.
  • 2 Institute of Biomedicine, Faculty of Health Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
  • 3 Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, and Maurice Wilkins Centre for Molecular Biodiscovery, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
  • 4 Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane 4072, Australia.
  • 5 Laboratory for Neuro-and Psychophysiology, Department of Neurosciences, & Leuven Brain Institute, KU Leuven, Leuven 3000, Belgium.
  • 6 ARC Centre for Innovation in Biomedical Imaging Technology, Centre for Advanced Imaging, The University of Queensland, Brisbane 4072, Australia.
  • 7 Nuclear Medicine and Molecular Imaging & MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven 3000, Belgium.
  • 8 Laboratory for Radiopharmaceutical Research, Department of Pharmacy and Pharmacological Sciences, KU Leuven, Leuven 3000, Belgium.
PMID: 36516997 DOI: 10.1021/acs.jmedchem.2c01485
Abstract

Multimodal imaging provides rich biological information, which can be exploited to study drug activity, disease associated phenotypes, and pharmacological responses. Here we show discovery and validation of a new probe targeting the endocannabinoid α/β-hydrolase domain 6 (ABHD6) Enzyme by utilizing positron emission tomography (PET) and matrix-assisted laser desorption/ionization (MALDI) imaging. [18F]JZP-MA-11 as the first PET ligand for in vivo imaging of the ABHD6 is reported and specific uptake in ABHD6-rich peripheral tissues and major brain regions was demonstrated using PET. A proof-of-concept study in nonhuman primate confirmed brain uptake. In vivo pharmacological response upon ABHD6 inhibition was observed by MALDI imaging. These synergistic imaging efforts used to identify biological information cannot be obtained by a single imaging modality and hold promise for improving the understanding of ABHD6-mediated endocannabinoid metabolism in peripheral and central nervous system disorders.

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