[11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson's disease: implications for the symptomatic threshold

Abstract

To estimate the threshold of nigrostriatal dysfunction required for symptomatic Parkinson's disease (PD), we employed [11C]RTI-32 and PET to study the dopamine transporter in striatal subdivisions of 11 L-dopa-naive patients with very early parkinsonism. As compared with the controls (N = 10), the PD group had on the side contralateral to the maximal clinical symptoms, significantly reduced binding in the posterior putamen (-56%) and anterior putamen (-28%), with the reduction in caudate (-12%) not significantly different. To the extent that dopamine transporter binding accurately reflects the number of nigrostriatal dopamine nerve terminals, these findings suggest that the clinical threshold for PD in the middle-age human is approximately 50% loss of dopaminergic innervation to the posterior putamen. Our data also suggest that damage to the putamen component of the striatum is sufficient for the clinical expression of PD.