Dopamine transporter binding inchronic manganese intoxication

Abstract. Chronic exposure to manganese may induce parkinsonismsimilar to idiopathic Parkinsons disease (PD). However,clinical manifestations of manganism also have some featuresdifferent from PD. The mechanisms of manganese-inducedparkinsonism remain not fully understood. ^99mTc-TRODAT-1 is a cocaine analoguethat can bind to the dopamine transporter (DAT) site reflectingthe function of presynaptic dopaminergic terminals. The purposeof this study was to evaluate DAT function using ^99mTc-TRODAT-1 to investigate theintegrity of the presynaptic dopaminergic terminals inmanganese-induced parkinsonism. Brain ^99mTc-TRODAT-1 single photon emissioncomputed tomography was performed in 4 patients with chronicmanganese intoxication in a ferromanganese smelting plant inTaiwan. Twelve PD patients and 12 healthy volunteers served asabnormal and normal controls, respectively. Clinically, allmanganism patients had a bradykinetic-rigid syndrome. The scoresof the Unified Parkinsons Disease Rating Scale ranged between19 and 64. The uptake values of the ^99mTc-TRODAT-1 were 0.868±0.136 inthe right corpus striatum and 0.865±0.118 in the left, ascompared with 0.951±0.059 and 0.956±0.058, respectively for thenormal controls. The data were significantly higher than0.250±0.070 and 0.317±0.066 respectively for the PD patients.Interestingly, there was a mild decrease in the uptake of ^99mTc-TRODAT-1 in the putamen and theratio of putamen and caudate when compared with the normalcontrols. Although the DAT shows a slight decrease in theputamen of manganism patients as compared with that of thenormal controls, the data indicate that the presynapticdopaminergic terminals are not the main target of chronicmanganese intoxication. In addition ^99mTc-TRODAT-1 SPECT can provide auseful, convenient and inexpensive tool for differentiationbetween chronic manganism and PD.