Disrupted Adenovirus-Based Anti-Cocaine Vaccine: Assessment Of Efficacy Based On Pet Dopamine Transporter (Dat) Imaging And Cocaine Challenge

412 Objectives We have recently developed a disrupted “adenovirus cocaine vaccine” (dAd5GNE) and preclinical studies have demonstrated that a standard prime-boost regimen of dAd5GNE evokes high titer anti-cocaine antibodies (anti-coc). In order to test the efficacy of dAd5GNE, we have performed DAT-PET in non-human primates, before and after vaccination using [11C]PE2I, a cocaine analog with high specificity to DAT. Methods Prior to vaccination, 4 rhesus monkeys had DAT-PET for 90 min with [11C]PE2I (5 mCi; SA: 10-15 Ci/μmole). At each session, DAT-PET was performed before and after cocaine challenge (1 mg/kg). Following vaccination with dAd5GNE, identical DAT-PET studies were repeated 2-3 times over a period of 4 months. Based on PET-MRI fused images and using the cerebellum as the reference region, PE2I binding potential (BP) for caudate and putamen were estimated for each PET study with and without cocaine challenge. Results Prior to vaccination, cocaine challenge significantly reduced PE2I BP (9.1±1.5 vs 4.0±1.0) and an estimated DAT occupancy was 55±12%. Following vaccination, cocaine challenge effects a significantly smaller reduction in BP (DAT occupancy Conclusions This primate study demonstrates that vaccination with dAd5GNE evokes high anti-coc titers sufficient to sequester iv administered cocaine in blood and preventing access to its receptors in the brain. DAT-PET with [11C]PE2I provides a reliable in vivo assay to assess the efficacy of dAd5GNE