In Vivo Detection of Monoaminergic Degeneration in Early Parkinson Disease by 18F-9-Fluoropropyl-(+)-Dihydrotetrabenzazine PET

Abstract

PET with (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-DTBZ), a novel radiotracer targeting vesicular monoamine transporter type 2 (VMAT2), has been proven as a useful imaging marker to measure dopaminergic integrity. The aim of this study was to evaluate the capability of (18)F-DTBZ PET in detecting the monoaminergic degeneration in early Parkinson disease (PD) in vivo. Seventeen age-matched healthy subjects and 30 PD patients at early stage of disease (duration of disease ≤ 5 y) with mild and unilateral motor symptoms underwent (18)F-DTBZ PET scans. The severity of disease, including Unified Parkinson Disease Rating Scale and modified Hoehn and Yahr Stage (mHY), were recorded at off-medication states. The standardized volumes of interest were applied to the spatial normalized image for quantification analysis. The specific uptake ratios (SURs) were calculated according to the formula (specific volumes-of-interest counts/occipital cortex counts) - 1. SUR measurements were summarized for each brain region. The mean duration of disease in the PD group was 3.2 ± 2.1 y (range, 0.5-5 y). The mean mHY was 1.0 ± 0.1 (range, 1-1.5). The SURs of bilateral caudate, anterior putamen, posterior putamen, substantia nigra, and nucleus accumbens were significantly lower in PD patients than those of healthy subjects. The reduction of SURs was most severe in the contralateral (the brain regions that are located opposite to the symptomatic side) posterior putamen (-81%), followed by the ipsilateral posterior putamen (-67%). Receiver-operating-characteristic curve analysis showed that the SURs of the bilateral posterior putamen and contralateral anterior putamen had a sensitivity of 100% and specificity of 100% in differentiating PD patients from healthy subjects. (18)F-DTBZ PET was as an excellent tool for the early diagnosis of PD. The obvious decline of (18)F-DTBZ uptake in the ipsilateral (asymptomatic) striatum suggested that (18)F-DTBZ PET might serve as an in vivo biomarker to detect the monoaminergic degeneration in the premotor phase of PD.