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

被引:3
作者
Mardon, Karine [1 ]
Patel, Jayendra Z. [2 ]
Savinainen, Juha R. [3 ]
Stimson, Damion H. R. [1 ]
Oyagawa, Caitlin R. M. [4 ,5 ]
Grimsey, Natasha L. [4 ,5 ]
Migotto, Mary-anne [1 ]
Njiru, Grace F. M. [1 ]
Hamilton, Brett R. [1 ,6 ]
Cowin, Gary [1 ]
Yli-Kauhaluoma, Jari [2 ]
Vanduffel, Wim [7 ,8 ]
Blakey, Idriss [1 ,9 ,10 ]
Bhalla, Rajiv [1 ]
Cawthorne, Christopher [11 ]
Celen, Sofie [12 ]
Bormans, Guy [12 ]
Thurecht, Kristofer J. [1 ,9 ,13 ]
Ahamed, Muneer [1 ,9 ,14 ]
机构
[1] Univ Queensland, Ctr Adv Imaging, Brisbane 4072, Australia
[2] Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Chem & Technol, FI-00014 Helsinki, Finland
[3] Univ Eastern Finland, Inst Biomed, Fac Hlth Sci, FI-70211 Kuopio, Finland
[4] Univ Auckland, Fac Med & Hlth Sci, Ctr Brain Res, Sch Med Sci,Dept Pharmacol & Clin Pharmacol, Auckland 1023, New Zealand
[5] Univ Auckland, Fac Med & Hlth Sci, Maurice Wilkins Ctr Mol Biodiscovery, Sch Med Sci, Auckland 1023, New Zealand
[6] Univ Queensland, Ctr Microscopy & Microanal, Brisbane 4072, Australia
[7] Katholieke Univ Leuven, Dept Neurosci, Lab Neuroand Psychophysiol, B-3000 Leuven, Belgium
[8] Katholieke Univ Leuven, Leuven Brain Inst, B-3000 Leuven, Belgium
[9] Univ Queensland, ARC Ctr Innovationin Biomed Imaging Technol, Ctr Adv Imaging, Brisbane 4072, Australia
[10] Univ Queensland, Australian Inst Bioengn & Nanotechnol AIBN, Nucl Med & Mol Imaging, Brisbane 4072, Australia
[11] Katholieke Univ Leuven, Dept Imaging & Pathol, MoSAIC, B-3000 Leuven, Belgium
[12] Katholieke Univ Leuven, Dept Pharm & Pharmacol Sci, Lab Radiopharmaceut Res, B-3000 Leuven, Belgium
[13] Univ Queensland, ARC Ctr Excellence Convergent Bionano Sci & Techno, Brisbane 4072, Australia
[14] South Australian Hlth & Med Res Inst SAHMRI, Mol Imaging & Therapy Res Unit MITRU & Natl Imagin, Adelaide, SA 5000, Australia
基金
英国医学研究理事会; 澳大利亚研究理事会; 芬兰科学院;
关键词
PRECLINICAL EVALUATION; CANNABINOID RECEPTOR; CB1; INHIBITORS; UREAS; OPTIMIZATION; RADIOTRACER; MECHANISM; SYSTEM; POTENT;
D O I
10.1021/acs.jmedchem.2c01485
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 alpha/beta-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.
引用
收藏
页码:538 / 552
页数:15
相关论文
共 57 条
[1]   Piperazine and Piperidine Triazole Ureas as Ultrapotent and Highly Selective Inhibitors of Monoacylglycerol Lipase [J].
Aaltonen, Niina ;
Savinainen, Juha R. ;
Ribas, Casandra Riera ;
Ronkko, Jani ;
Kuusisto, Anne ;
Korhonen, Jani ;
Navia-Paldanius, Dina ;
Hayrinen, Jukka ;
Takabe, Piia ;
Kasnanen, Heikki ;
Pantsar, Tatu ;
Laitinen, Tuomo ;
Lehtonen, Marko ;
Pasonen-Seppanen, Sanna ;
Poso, Antti ;
Nevalainen, Tapio ;
Laitinen, Jarmo T. .
CHEMISTRY & BIOLOGY, 2013, 20 (03) :379-390
[2]   Synthesis and preclinical evaluation of [11C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL) [J].
Ahamed, Muneer ;
Attili, Bala ;
van Veghel, Daisy ;
Ooms, Maarten ;
Berben, Philippe ;
Celen, Sofie ;
Koole, Michel ;
Declercq, Lieven ;
Savinainen, Juha R. ;
Laitinen, Jarmo T. ;
Verbruggen, Alfons ;
Bormans, Guy .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 136 :104-113
[3]  
[Anonymous], High-Resolution Image Synthesis with Latent Diffusion Mod
[4]   Preclinical evaluation of [18F]MA3: a CB2 receptor agonist radiotracer for PET [J].
Attili, Bala ;
Celen, Sofie ;
Ahamed, Muneer ;
Koole, Michel ;
Van Den Haute, Chris ;
Vanduffel, Wim ;
Bormans, Guy .
BRITISH JOURNAL OF PHARMACOLOGY, 2019, 176 (10) :1481-1491
[5]   2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain [J].
Baggelaar, Marc P. ;
Maccarrone, Mauro ;
van der Stelt, Mario .
PROGRESS IN LIPID RESEARCH, 2018, 71 :1-17
[6]   Chemical Proteomics Maps Brain Region Specific Activity of Endocannabinoid Hydrolases [J].
Baggelaar, Marc P. ;
van Esbroeck, Annelot C. M. ;
van Rooden, Eva J. ;
Florea, Bogdan I. ;
Overkleeft, Herman S. ;
Marsicano, Giovanni ;
Chaouloff, Francis ;
van der Stelt, Mario .
ACS CHEMICAL BIOLOGY, 2017, 12 (03) :852-861
[7]   Identification of [18F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging [J].
Bernard-Gauthier, Vadim ;
Mossine, Andrew V. ;
Mahringer, Anne ;
Aliaga, Arturo ;
Bailey, Justin J. ;
Shao, Xia ;
Stauff, Jenelle ;
Arteaga, Janna ;
Sherman, Phillip ;
Grand'Maison, Marilyn ;
Rochon, Pierre-Luc ;
Waengler, Bjoern ;
Waengler, Carmen ;
Bartenstein, Peter ;
Kostikov, Alexey ;
Kaplan, David R. ;
Fricker, Gert ;
Rosa-Neto, Pedro ;
Scott, Peter J. H. ;
Schirrmacher, Ralf .
JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (04) :1737-1743
[8]   Advances in mass spectrometry imaging enabling observation of localised lipid biochemistry within tissues [J].
Bowman, Andrew P. ;
Heeren, Ron M. A. ;
Ellis, Shane R. .
TRAC-TRENDS IN ANALYTICAL CHEMISTRY, 2019, 120
[9]   Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation [J].
Cabral, Guy A. ;
Griffin-Thomas, LaToya .
EXPERT REVIEWS IN MOLECULAR MEDICINE, 2009, 11
[10]  
Cao J. K., 2021, J NEUROL NEUROL DISO, V7, P106