Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

被引：6
作者：
Teodoro, Rodrigo [1 ]
Guendel, Daniel [1 ]
Deuther-Conrad, Winnie [1 ]
Ueberham, Lea [1 ]
Toussaint, Magali [1 ]
Bormans, Guy [2 ]
Brust, Peter [1 ,3 ]
Moldovan, Rares-Petru [1 ]
机构：
[1] Helmholtz Zentrum Dresden Rossendorf HZDR, Dept Neuroradiopharmaceut, Inst Radiopharmaceut Canc Res, Res Site Leipzig, D-04318 Leipzig, Germany
[2] Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Radiopharmaceut Res, BE-3000 Leuven, Belgium
[3] Univ Med Ctr Schleswig Holstein, Lubeck Inst Expt Dermatol, D-23562 Lubeck, Germany
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 15期
关键词：
cannabinoid receptor type 2; naphtyrid-2-one; binding affinity; radiochemistry; fluorine-18; labelling; brain; positron emission tomography; IN-VIVO EVALUATION; CB2; RECEPTORS; PRECLINICAL EVALUATION; ALZHEIMERS-DISEASE; HIGH-AFFINITY; RADIOTRACER; DERIVATIVES; EXPRESSION; LIGANDS; TRACER;
D O I：
10.3390/ijms22158051
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we herein describe the radiosynthesis of cis-[F-18]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([F-18]LU14) starting from the corresponding mesylate precursor. The first biological evaluation revealed that [F-18]LU14 is a highly affine CB2R radioligand with >80% intact tracer in the brain at 30 min p.i. Its further evaluation by PET in a well-established rat model of CB2R overexpression demonstrated its ability to selectively image the CB2R in the brain and its potential as a tracer to further investigate disease-related changes in CB2R expression.
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页数：18
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