1. Academic Validation
  2. Radiolabeling of the cannabinoid receptor agonist AZD1940 with carbon-11 and PET microdosing in non-human primate

Radiolabeling of the cannabinoid receptor agonist AZD1940 with carbon-11 and PET microdosing in non-human primate

  • Nucl Med Biol. 2013 Apr;40(3):410-4. doi: 10.1016/j.nucmedbio.2012.10.011.
Magnus Schou 1 Katarina Varnäs Aurelija Jucaite Balázs Gulyás Christer Halldin Lars Farde
Affiliations

Affiliation

  • 1 AstraZeneca Translational Sciences Centre, PET CoE, Dept of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, SE-17176 Stockholm, Sweden. magnus.schou@astrazeneca.com
Abstract

Introduction: N-(2-tert-butyl-1-((4,4-difluorocyclohexyl)methyl)-1H-benzo[d]imidazol-5-yl)ethanesulfonamide (AZD1940) is a candidate drug for treatment of neuropathic pain. As part of the preclinical evaluation of AZD1940, a microdosing study with positron emission tomography (PET) was conducted to assess brain exposure.

Methods: AZD1940 was radiolabeled with carbon-11 in the benzimidazole moiety. The radioactive precursor, lithium [(11)C]pivalate was obtained via (11)C-carboxylation of tert-butyl lithium. The target compound, [(11)C]AZD1940, was in turn obtained by the microwave assisted reaction between lithium [(11)C]pivalate and the o-phenylene diamine analog of AZD1940 (N-(3-amino-4-((4,4-difluorocyclohexyl)methylamino)phenyl)ethanesulfonamide) in neat phosphorous oxychloride. A brain PET measurement was performed in cynomolgus monkey.

Results: The overall radiochemical yield of final formulated radiochemically pure (>99%) [(11)C]AZD1940 was 0.4% (uncorrected for decay) and the specific radioactivity was 13GBq/μmol at time of administration (58min after end of bombardment). After intravenous injection to cynomolgus monkey, the maximum concentration of radioactivity detected in the brain region of interest was 0.7% of the total injected radioactivity. The regional distribution of radioactivity within brain was homogenous.

Conclusions: AZD1940 was radiolabelled with carbon-11 and its brain exposure, assessed using PET, was relatively low in comparison to peripheral organ exposure.

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