MPTP-induced up-regulation of in vivo dopaminergicradioligand-receptor binding in humans

We measured in vivo dopaminergic receptor binding usingpositron emission tomography and ¹⁸F-spiperone in an untreated symptomatic subject with MPTP-induced parkinsonism. Our technique determines four variables related to entry of ¹⁸F-spiperone into brain tissue and subsequent binding to receptors: (1) the combined forward-rate constant k₁′ (equal to the product of the maximum number of available specific binding sites, B_max, times the association rate constant [k_a] of ¹⁸F-spiperone and receptor); (2) the binding site dissociation rate constant k-₁; (3) the free fraction of radioligand not specifically bound in brain tissue, f₂; and (4) the regional permeability-surface-area product (PS) of the blood-brain barrier for spiperone. PS and f₂ in the patient were not different from that of 10 normal volunteers, whereas the combined forward-rate constant (left caudate: k₁′ = 67.6 sec⁻¹, normal = 0.140 ± 0.056) and the dissociation rate constant (left caudate: k₋₂ = 0.116 sec^-1, normal = 0.000339 ± 0.000149) were elevated. These findings provide potential new insights not only into the pathophysiology of this disease but into the clinical importance of dopamine receptor function as well.