In vivo quantification of dopaminergic terminals loss in Parkinson’s Disease rat with AAV-induced overexpression of alpha-synuclein: a [18F]FMT microPET study.

Objectives: Rat models of Parkinson’s disease (PD), such as progressive neurodegeneration induced by adeno-associated virus (AAV)-mediated over-expression of human -synuclein (A53T) in midbrain dopamine neurons, are useful to evaluate novel antiparkinsonian therapies [1]. In vivo quantitative imaging of dopamine neurotransmission allows longitudinal evaluation of such PD’s rat model [2]. In this study, we investigate DA presynaptic function, with [18F]FMT PET (radiotracer of the L-aromatic amino acid decarboxylase enzyme), in the AAV A53T PD’s rat model, and correlate the results with behavioral measurements. Methods: All animals were injected with 2 µL A53T -synuclein (n=6) or GFP (n=2) AAV2/9 in the right substantia nigra. Striatal DA presynaptic activity was assessed by dynamic PET with [18F]FMT [3] at 18 weeks post-lesion. Kinetic analysis was performed by “Patlak Reference” model, using PMOD software. Rats were monitored for motor behavior and assessed before the lesion, and at 4, 12 and 18 weeks post-lesion. Results: As consequence of AAV-mediated A53T overexpression, significant decrease of [18F]FMT accumulation was recorded in the striatum ipsilateral to the lesion. Lesioned rats had dramatically reduced uptake constant Ki in the ipsilateral striatum compared to the contralateral striatum (p<0.001 for [18F]FMT) and to the ipsilateral striatum of sham-treated rats (p