Quantitative [(123)I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson's disease.

Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [(123)I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra. To assess this question experimentally, we studied two different mouse models of PD, namely a mild 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication paradigm, to model mild nigrostriatal damage and the intrastriatal 6-hydroxydopamine paradigm to model more advanced nigrostriatal damage. Our data demonstrate that the striatal [(123)I]FP-CIT binding measured by SPECT in vivo precisely predicts the striatal dopamine concentrations, but does not necessarily correlate with the nigral dopaminergic cell number. Thus, the present work underscores that FP-CIT SPECT does only allow judging the integrity of the striatal dopaminergic nerve terminals, but not the nigral dopaminergic cells in PD. This finding may have significant impact on the use of [(123)I]FP-CIT SPECT as a surrogate marker for clinical trials aimed at measuring neuroprotection.