Objective: To provide first evidence of in vivo binding properties of the [¹⁸F]SynVesT-1 tracer (aka [¹⁸F]-SDM-8) for the quantification of synaptic density loss in a Parkinson’s disease (PD) patient and in the postmortem brain of a Multiple System Atrophy (MSA) patient.

Background: The [¹¹C]UCB-J tracer has been used to explore the synaptic density loss in PD (1–3). Recently, the synaptic vesicle protein 2A (SV2A) radioligand [18F]SynVesT-1 has been tested in healthy controls (4), and to date, there are no studies in parkinsonian patients.

Method: In vivo imaging: Two healthy controls (HC1: female, 50y; HC2: male, 67y) and one PD patient (66y, 15y disease duration, MDS-UPDRS-III=34, H&Y=3) were scanned. PET scans were acquired on a GE Discovery MI PET-CT. The radiotracer was injected via bolus injection (range 183-191MBq), and emission data acquired for 120 min with arterial blood collection. Low dose CT images were used for attenuation correction, and dynamic image reconstruction was performed using filtered back-projection. PET images were matched to the subject’s T1-weighted MRI and processed using Pmod 4.2. For this analysis, we applied a Simplified Reference Tissue Model 2 (SRTM2) to compute BP_ND values with the Centrum Semiovale as reference region (5).
Postmortem imaging: The [¹⁸F](R)-SDM8 in vitro binding was assessed in the striatum and occipital lobe of a MSA patient. Sections were sliced at 10 µm and stored at -80°C. Slides were thawed and dried at room temperature for at least 30 minutes. Tissue was incubated for 1h with [¹⁸F](R)-SDM8 (2nM and 12,400 mCi/µmole) or with 200µM levetiracetam.

Results: Whole-brain BP_ND maps for the healthy controls and PD are shown in Fig.1 displaying distribution of BP_ND in the cortical and subcortical regions. Fig.2 shows the postmortem in vitro binding in sections of the striatum and occipital lobe of the MSA patient with [¹⁸F](R)-SDM8 and following levetiracetam.

Conclusion: The preliminary data with the [¹⁸F] labeled SV2A tracer displayed good in vivo binding distribution properties in PD, and postmortem MSA patient. The use of the [¹⁸F]SynVesT-1 tracer is a promising tool for synaptic density quantification in parkinsonism.

References: 1. Matuskey D, Tinaz S, Wilcox KC, Naganawa M, Toyonaga T, Dias M, et al. Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging. Ann Neurol. 2020;87(3):329–38.
2. Delva A, Van Weehaeghe D, Koole M, Van Laere K, Vandenberghe W. Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson’s Disease. Mov Disord. 2020;35(11):1977–86.
3. Wilson H, Pagano G, de Natale ER, Mansur A, Caminiti SP, Polychronis S, et al. Mitochondrial Complex 1, Sigma 1, and Synaptic Vesicle 2A in Early Drug-Naive Parkinson’s Disease. Mov Disord. 2020;35(8):1416–27.
4. Naganawa M, Li S, Nabulsi N, Henry S, Zheng MQ, Pracitto R, et al. First-in-Human Evaluation of 18 F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A. J Nucl Med. 2021;62(4):561–7.
5. Naganawa M, Gallezot JD, Li S, Nabulsi NB, Henry S, Zheng MQ, et al. Noninvasive quantification of 18F-SynVesT-1 binding using simplified reference tissue model 2. [Abstract] Society of Nuclear Medicine and Molecular Imaging (SNMMI). 2022.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-synaptic-density-in-parkinsonism/