MPTP-induced up-regulation of in vivo dopaminergic radioligand-receptor binding in humans

Abstract

We measured in vivo dopaminergic receptor binding using positron 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, Bmax, times the association rate constant [ka] 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-1 = 0.116 sec-1, normal = 0.000339 +/- 0.000149) were evaluated. 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.