Dataset Open Access
Teodoro, Rodrigo; Gündel, Daniel; Deuther-Conrad, Winnie; Toussaint, Magali; Wenzel, Barbara; Bormans, Guy; Kopka, Klaus; Brust, Peter; Moldovan, Rares-Petru
{ "type": "dataset", "id": "2252", "DOI": "10.14278/rodare.2252", "author": [ { "family": "Teodoro, Rodrigo" }, { "family": "G\u00fcndel, Daniel" }, { "family": "Deuther-Conrad, Winnie" }, { "family": "Toussaint, Magali" }, { "family": "Wenzel, Barbara" }, { "family": "Bormans, Guy" }, { "family": "Kopka, Klaus" }, { "family": "Brust, Peter" }, { "family": "Moldovan, Rares-Petru" } ], "abstract": "<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>", "title": "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", "publisher": "Rodare", "issued": { "date-parts": [ [ 2023, 4, 5 ] ] } }
All versions | This version | |
---|---|---|
Views | 148 | 148 |
Downloads | 705 | 705 |
Data volume | 158.8 MB | 158.8 MB |
Unique views | 136 | 136 |
Unique downloads | 534 | 534 |