In vivo evaluation of [¹²³I]MNI-420: A novel single photon emission computed tomography radiotracer for imaging of adenosine 2A receptors in brain

Introduction: Dysregulation of adenosine 2A (A_2A) receptor function in brain has been implicated in multiple psychiatric and neurodegenerative disorders, including schizophrenia and Parkinson's disease, making the development of an imaging agent to study A_2A receptors in both healthy brain and disease states desirable. In this study, [¹²³I]MNI-420 was evaluated as a potential single photon emission computed tomography (SPECT) radiotracer for imaging A_2A receptors in brain. Methods: Two adult male monkeys (Macaca fascicularis) and three adult female baboons (Papio anubis) were anesthetized and imaged on Neurofocus SPECT cameras. Baboons underwent baseline and displacement studies using varying doses of caffeine (2.0-20mg/kg). Baseline and pre-blocking experiments with multiple doses of preladenant (0.01-1.2mg/kg), a highly selective A_2A antagonist, were performed in cynomolgus monkeys. Results: Following bolus intravenous (i.v.) injection, [¹²³I]MNI-420 rapidly entered the non-human primate brain. The regional brain accumulation of [¹²³I]MNI-420 matched the known distribution of A_2A receptors in brain (highest in the striatum). Striatum to cerebellum ratios and binding potentials of around 3.0-3.5 and 2.0-2.5, respectively, were measured in monkey and baboon brain. A dose-dependent occupancy was observed following i.v. injection of caffeine at pseudo-equilibrium conditions during displacement experiments. Pre-treatment with preladenant blocked specific binding in A_2A rich regions in a dose-dependent fashion. Conclusions: The data indicate that [¹²³I]MNI-420 holds promise as a SPECT radiotracer for imaging A_2A receptors in brain and further evaluation is warranted, in order to determine its utility as a SPECT radiotracer for imaging of A_2A in brain.