2026-05-24T15:55:44Z
https://rodare.hzdr.de/oai2d
oai:rodare.hzdr.de:2252
2023-05-04T16:56:32Z
openaire_data
user-rodare
true
3.1
HZDR.RODARE
10.14278/rodare.2252
Teodoro, Rodrigo
0000-0002-1425-0567
Gündel, Daniel
0000-0001-9743-2325
Deuther-Conrad, Winnie
0000-0003-3168-3062
Toussaint, Magali
0000-0002-1136-3857
Wenzel, Barbara
0000-0001-7390-3575
Bormans, Guy
Kopka, Klaus
0000-0003-4846-1271
Brust, Peter
0000-0001-5555-7058
Moldovan, Rares-Petru
0000-0003-3119-7945
Data publication: Enantioselective Synthesis, Structure Activity Relationship, Radiofluorination and Biological Evaluation of [18F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET
Rodare
2023
cannabinoid receptor type 2
indole-2-carboxamide
binding affinity
radiochemistry
fluorine-18 labeling
positron-emission tomography
2023-04-05
https://rodare.hzdr.de/record/2252
https://www.hzdr.de/publications/Publ-36778
https://www.hzdr.de/publications/Publ-35005
10.14278/rodare.2251
https://rodare.hzdr.de/communities/rodare
Creative Commons Attribution 4.0 International
Open Access
<p>The development of cannabinoid receptor type 2 (CB2R) PET radioligands has been intensively explored due to the pronounced CB2R upregulation in various pathological conditions, such as neuroinflammation and cancer. Herein we report on the enantioselective synthesis of a series of highly affine fluorinated indole-2-carboxamide ligands targeting the CB2R in the brain. Compound RM365 was selected for PET radiotracer development due to its high CB2R affinity (Ki = 2.1 nM) and pronounced selectivity over CB1R (factor > 300). A fully automated copper-mediated radiofluorination of [18F]RM365 was established starting from the corresponding aryl boronic acid pinacol ester precursor. Preliminary in vitro evaluation of [18F]RM365 indicated species differences in the binding to CB2R (KD of 2.32 nM for the human CB2R vs. KD > 10000 nM for the rat CB2R). Metabolism studies in mice revealed high stability of [18F]RM365 with fractions of parent compound of > 90% in the brain and > 54% in the plasma at 30 min p.i. PET imaging in a rat model of local hCB2R(D80N) overexpression in the brain demonstrate the ability of [18F]RM365 to reach and selectively label the intracranial expressed hCB2R(D80N) with high signal-to-background ratio. Thus, [18F]RM365 is a very promising PET radioligand for the imaging of upregulated hCB2R expression under pathological conditions with high potential towards clinical application in humans.</p>