RT Journal Article
SR Electronic
T1 <strong>Copper-mediated automated radiofluorination and </strong><strong>biological evaluation</strong><strong> of </strong><strong>a highly affine cannabinoid receptor type 2 ligand with PET</strong><strong/>
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 197
OP 197
VO 61
IS supplement 1
A1 Rodrigo Teodoro
A1 Magali Toussaint
A1 Daniel Gundel
A1 Winnie Deuther-Conrad
A1 Barbara Wenzel
A1 Peter Brust
A1 Rares-Petru Moldovan
YR 2020
UL http://jnm.snmjournals.org/content/61/supplement_1/197.abstract
AB 197Introduction: 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. Herein we report on the development of a series of highly affine fluorinated indole-carbamate ligands targeting the CB2R in the brain. Starting from an arylboronic ester precursor, a copper-mediated automated radiofluorination was developed and preliminary biological evaluation was carried out for the most promising ligand. Methods: A series of fifteen indole-carbamate derivatives was synthesized and their binding affinities (Ki) towards CB2R were determined. Compound RM365 was selected for PET radiotracer development due to its high CB2R affinity (KiCB2 = 2.1 nM) and pronounced selectivity over CB1R (factor &gt;300). A fully automated copper-mediated radiofluorination of [18F]RM365 was established starting with the corresponding arylboronic ester precursor. The metabolic stability of [18F]RM365 was investigated in plasma and brain samples (CD1 mice, 30 min p.i) by radio&amp;#8209;HPLC. PET studies with [18F]RM365 were performed under baseline conditions (60 min scan). Results: [18F]RM365 was obtained with a moderate radiochemical yield of about 5% and high radiochemical purities (&gt;98%). PET studies revealed that [18F]RM365 readily crossed the blood-brain barrier and accumulated in the spleen, a CB2R-rich organ. Metabolite studies showed that 55% and 90% of the total extracted activity accounted for the amount of parent tracer, in plasma and brain samples respectively. Conclusions: A fully automated copper-mediated radiosynthesis was established for [18F]RM365. Further blocking experiments will demonstrate the CB2R specificity of [18F]RM365 in vivo and will be used as a pass-fail criterion for further application of the radiotracer in CB2R-related animal models. Acknowledgments: This work has been supported by the DFG (project MO 2677/4-1).