99mTc-TRODAT-1 SPECT in healthy and 6-OHDA lesioned parkinsonian monkeys: comparison with 18F-FDOPA PET

Abstract

Parkinson's disease (PD) is a degeneration of the nigrostriatal dopaminergic pathway, leading to a selective loss of dopamine in the striatum. 99mTc-TRODAT-1 is a recently developed radiotracer that selectively binds to the dopamine transporters, which are significant because loss of these transporters corresponds with a loss of dopaminergic neurons. The present investigation compared 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) with 18F-FDOPA positron emission tomography (PET) in the evaluation of PD using a primate model. Three monkeys, including one 6-hydroxydopamine lesioned PD model and two controls, were examined by both 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET. For the PD monkey, expression of parkinsonian behaviour and 18F-FDOPA PET were used to evaluate the severity of the lesion. 99Tc-TRODAT-1 was prepared from a lyophilized kit. After intravenous injection of the radiotracer, SPECT was acquired over 4 h using a dual-head camera equipped with ultra-high resolution fan-beam collimators. Both uptake measurement and visual assessment were performed. Data were compared with motor behaviour and PET imaging. The striatal uptake in both healthy and PD monkeys increased continuously during the study, although the gradient of increase was less prominent in the diseased monkey. The increased uptake in the controls appeared to become blunt around 4 h after injection. A profound decrease of 99Tc-TRODAT-1 uptake was found in the striatum of the PD monkey compared with the controls (0.91 vs 2.16). In the PD monkey, the decrease of striatal uptake contralateral to the more affected side of the body was more prominent compared to the ipsilateral side (0.77 vs 1.06). In addition, greater loss occurred in the contralateral side of the putamen (0.54 vs 1.04). Changes of uptake ratios in the striatum and its subnuclei of the PD monkey were significantly correlated with those measured from PET. The loss of striatal uptake appeared greater in SPECT than the corresponding PET with both visual and uptake analyses. In conclusion, our data in a limited series of cases indicate that 99Tc-TRODAT-1 with a conventional nuclear medicine camera system may provide a suitable tool in evaluating parkinsonism in a primate model.