Positron emission tomography (PET) coupled to 6-[¹⁸F]Fluoro-L-Dopa (¹⁸F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, ¹¹C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. ¹¹C-PE2I B′max values obtained with this approach were compared with ¹⁸F-Dopa input rate constant values (Ki), in vitro Bmax binding of ¹²⁵I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for ¹¹C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B′max = 26 and 36 pmol/mL) and reserpine-treated animals (B′max = 338 and 483 pmol/mL). In vivo¹¹C-PE2I B′max values correlated with ¹⁸F-Dopa Ki values and in vitro¹²⁵I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of ¹¹C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.