Detection of dopaminergic cell loss and neural transplantation using pharmacological MRI, PET and behavioral assessment

WE: demonstrate the use of magnetic resonance imaging (MRI) for detection o f neurotransmitter stimulation using the dopamine transporter ligands amphe tamine and CFT (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane)'ias pha rmacological challenges, We demonstrate that the unilateral loss of a hemod ynamic response to either amphetamine or CFT challenge by unilateral 6-hydr oxydopamine lesioning is restored by transplantation of fetal dopamine neur ons in the striatum,The time course for the hemodynamic changes parallels t he time-courses for dopamine release, measured by prior microdialysis studi es, and also for the rotational behavior in the unilaterally lesioned anima ls. Transplantation of the fetal cells results in hemodynamic time courses after CFT or amphetamine challenges at the graft Site that are identical to those induced both before transplantation and on the intact contralateral side. The:transplantation also results in complete behavioral recovery. The spatial extent of the dopaminergic recovery: in the lesioned striatum is t he same when measured using either PET of tracer levels of [C-11]CFT bindin g or MRI. These results show great promise for the application of pharmacol ogical MRI for application to studies Of dopamine cell loss and potential r ecovery in Parkinson's disease. (C) 1999 Lippincott Williams & Wilkins.