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Abstract Details

Measuring Synaptic Density and Dopamine Transporter Availability in Parkinson's Disease: A PET Imaging Study with 11C-UCB-J and 18F-FE-PE2I
Movement Disorders
P7 - Poster Session 7 (11:45 AM-12:45 PM)
3-007
To relate synaptic density and presynaptic dopaminergic terminal integrity along the nigrostriatal tract using in vivo PET imaging in individuals with Parkinson's disease (PD) and healthy controls (HCs).
The pathophysiology of PD involves the degeneration of dopaminergic neurons in the substantia nigra, leading to reduced striatal dopamine signaling. This study employs 11C-UCB-J, targeting synaptic vesicle glycoprotein 2A (SV2A), to assess presynaptic loss, and 18F-FE-PE2I, a highly selective dopamine transporter (DaT) ligand, to evaluate dopaminergic loss.

Twenty PD patients (11 women, 61.0±5.3 years) and thirteen HCs (7 women, 57.8±5.4 years) underwent PET imaging with 11C-UCB-J and 18F-FE-PE2I on separate days using a high-resolution research tomograph (HRRT). Binding potential (BPND) was quantified employing the Simplified Reference Tissue Model 2 (SRTM2) with the cerebellum as a reference region for 18F-FE-PE2I and the centrum semiovale for 11C-UCB-J. Four regions of interest (ROIs) (caudate, substantia nigra, putamen, ventral striatum) were delineated from a standardized template. Across-subject Spearman correlations between 11C-UCB-J and 18F-FE-PE2I BPND values were computed and corrected for false discovery rate (FDR). For the PD group, correlations with motor severity scores (i.e., MDS-UPDRS part III) were also explored.
In the PD group, a significant positive correlation between 11C-UCB-J and 18F-FE-PE2I BPND was observed in the caudate (r=0.59,p-FDR=0.02), but not in the other regions. This correlation remained significant (p-FDR<0.05) even after controlling for covariates (i.e., age, gender, BMI, and the interval between scans) via partial correlation.  Additionally, there was a trend toward significance in the caudate and substantia nigra in HCs (r=0.62 and r=0.61,p-FDR=0.06 for both), but not if covariates were accounted for. A negative relationship between 18F-FE-PE2I putamen BPND and MDS-UPDRS part III was also observed (r=-0.79,p-FDR=5·10-4). 

Our findings point to a clinically meaningful relationship between striatal DaT binding and synaptic density, and its impact on PD clinical symptoms needs to be further elucidated.
Authors/Disclosures
Faranak Ebrahimian Saadabad
PRESENTER 		Mr. Ebrahimian Saadabad has nothing to disclose.
Tommaso Volpi Tommaso Volpi has nothing to disclose.
Praveen Honhar Praveen Honhar has nothing to disclose.
Mika Naganawa Mika Naganawa has nothing to disclose.
Salih Cayir Mr. Cayir has nothing to disclose.
Sule Tinaz No disclosure on file
Jean-Dominique Gallezot The institution of Jean-Dominique Gallezot has received research support from Intra-cellular Therapies, Inc.. The institution of an immediate family member of Jean-Dominique Gallezot has received research support from Cerevel.
Gustavo Angarita (Yale University) Gustavo Angarita has nothing to disclose.
Sophie Holmes (Yale university) No disclosure on file
Richard E Carson The institution of Richard E Carson has received research support from Cerevel. The institution of Richard E Carson has received research support from Pfizer.
Sjoerd J. Finnema (Abbvie) Sjoerd J. Finnema has received personal compensation for serving as an employee of AbbVie. Sjoerd J. Finnema has stock in AbbVie.
David Matuskey, MD (Yale University) Dr. Matuskey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Eleisver. The institution of Dr. Matuskey has received research support from Abbvie.