TY - JOUR T1 - <strong>Interaction of Striatal Dopaminergic and Cholinergic Activity in Parkinson Disease: A Multimodal Imaging Study Based on <sup>11</sup>C-DTBZ and <sup>18</sup>F- FEOBV PET Combined with Diffusion Tensor Imaging</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 600 LP - 600 VL - 61 IS - supplement 1 AU - Carlos Sanchez-Catasus AU - Martijn Muller AU - Nicholas D'cruz AU - Prabesh Kanel AU - Nicolaas I. Bohnen Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/600.abstract N2 - 600Objectives: Parkinson Disease (PD) is characterized by alpha-synucleinopathy and Lewy pathology leading to neuronal cell loss. Recent evidence suggests that axonal and synaptic dysfunction may occur before the degenerative loss of nigral neuronal cell bodies in PD (1). Striatal dopaminergic loss in PD has been associated with compensatory changes in striatal cholinergic interneurons, at least in early stages of the disease, however the relationship of these interacting changes with PD phenotypes is unknown. 11C-DTBZ and 18F-FFEOBV both bind selectively to the vesicular transporters of the monoaminergic and cholinergic systems, respectively, and reflect nerve terminal integrity. Aims: The purpose of this study was to examine the relationship between striatal dopaminergic and cholinergic nerve terminal integrity and microstructural integrity of associated tracts using diffusion tensor imaging (DTI) and its association with PD phenotype. Methods: This study included 48 PD patients grouped according to the clinical phenotype: 28 tremor-dominant (TD) patients (age: 66.1 ± 6.1 years; gender: 22 males; disease duration: 6.0 ± 3.8 years; Hoehn and Yahr (HY) stage: 2.0 ±0.6; UPDRS part III motor score: 31.9 ± 13.7) and 20 patients with postural instability and gait disorder (PIGD) phenotype (age: 66 ± 6.2 years; 12 males; disease duration: 6.7± 4.7 years; HY stage: 2.7 ±0.5; UPDRS part III motor score: 35.4 ± 14.3). 11C-DTBZ and 18F-FEOBV PET was performed following standard procedures. DTI was performed to assess fractional anisotropy (FA; a measure of tract integrity) of tracts correlated with dopaminergic (11C-DTBZ) and cholinergic-activity (18F-FEOBV). Tractography was based on a deterministic fiber tracking algorithm using the DSI Studio toolbox. Results: No significant association was found between striatal 11C-DTBZ and 18F-FEOBV PET binding for either group or both groups combined (TD: Spearman correlation rho= -0.06, p= 0.8; PIGD: rho= 0.12, p= 0.6; ALL: rho= -0.08 p= 0.6). Multimodal DTI-PET analysis showed that FA of specific striatal tracts positively correlated with striatal 11C-DTBZ binding in both groups (TD, Figures 1.A and 1.B, rho= 0.51, p= 0.005; PIGD, Figures 1.E and 1.F, rho= 0.60, p= 0.005). Similar results were found for the association between FA of striatal tracts and striatal 18F-FEOBV binding (TD, Figures 1.A and 1.C, rho= 0.40, p= 0.03; PIGD, Figures 1.E and 1.G, rho= 0.45, p= 0.045). For the TD group there was a positive correlation between FA of striatal 11C-DTBZ and striatal 18F-FEOBV related tracts (Figure.1. D, rho= 0.54, p= 0.02) while this correlation was negative for the PIGD group (Figure.1.H, rho= -0.44, p= 0.048). Conclusions: Our results suggest that multimodal PET analysis based on 11C-DTBZ and 18F-FEOBV PET combined with DTI provides evidence of a relationship between neurotransmitter nerve terminal integrity and axonal integrity. Analysis of the clinical phenotypes showed a differential relationship between tracts associated with DA and ACh nerve terminals. These findings suggest that PD phenotype, in part, may be driven by changes in the interaction between striatal dopaminergic and cholinergic systems. 1. Bridi JC, Hirth F. Mechanisms of α-Synuclein Induced Synaptopathy in Parkinson's Disease. Front Neurosci. 2018;12:80.doi: 10.3389/fnins.2eCollection 2018. ER -