Radiosynthesis and in vivo evaluation of a novel σ₁ selective PET ligand.

ABSTRACT: The σ₁ receptor is an important target for CNS disorders. We previously identified a σ₁ ligand TZ3108 having highly potent (K_i-σ1 = 0.48 nM) and selective affinity for σ₁ versus σ₂ receptors. TZ3108 was ¹⁸F-labeled with F-18 for in vivo evaluation. Biodistribution and blocking studies of [¹⁸F]TZ3108 in male Sprague-Dawley rats demonstrated high brain uptake, which was σ₁-specific with no in vivo defluorination. MicroPET studies in cynomolgus macaques showed high brain penetration of [¹⁸F]TZ3108; the regional brain distribution was consistent with that of the σ₁ receptor. Pseudo-equilibrium in the brain was reached ~ 45 min post-injection. Metabolite analysis of

SUBMITTER: Jin H 

PROVIDER: S-EPMC4288033 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature