In vivo PET imaging in rat of dopamine terminals reveals functional neural transplants

Abstract

Positron emission tomography (PET) and carbon-11-labeled 2B-carbomethoxy-3B-(4-fluorophenyl)tropane (11C-CFT or 11-WIN 35,428) were used as molecular markers for striatal presynaptic dopamine (DA) transporters in a unilateral Parkinson's disease rat neurotransplantation model. In the lesioned striatum, the binding ratio measured by the DA presynaptic marker was reduced to 15% to 35% of the intact side (or unoperated control). After grafting with non-DA cells (from dorsal mesencephalon), the DA binding ratio remained reduced to levels observed before transplantation and rats showed no behavioral recovery. In contrast, after DA neuronal transplantation, behavioral recovery occurred only after the 11C-CFT binding ratio had increased to 75% to 85% of the intact side. This study provides direct in vivo evidence for the dopaminergic molecular basis of functional recovery in the lesioned nigrostriatal system after neural transplantation.