Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
Institute of Nuclear Medicine and Molecular, Imaging of Zhejiang University, Hangzhou, Zhejiang, 310009, China.
Eur J Nucl Med Mol Imaging. 2024 Dec;52(1):158-170. doi: 10.1007/s00259-024-06904-6. Epub 2024 Aug 28.
[F]SynVesT-1 is a novel radiopharmaceutical for assessing synaptic density in vivo. This study aims to investigate the potential of [F]SynVesT-1 positron emission tomography (PET) in evaluating neurological recovery in the rat model of ischemic stroke, and to compare its performance with [F]FDG PET.
Sprague-Dawley rats were subjected to photothrombotic cerebral infarction, and safinamide was administered intraperitoneally from day 3 to day 14 post-stroke to alleviate neurological deficits. Cylinder test and forelimb placing test were performed to assess the neurological function. MRI, [F]SynVesT-1 PET/CT and [F]FDG PET/CT imaging were used to evaluate infarct volume, synaptic density, and cerebral glucose metabolism pre- and post-treatment. [F]SynVesT-1 and [F]FDG PET images were compared using Statistical Parametric Mapping (SPM) and region of interest (ROI)-based analysis. Post-mortem histological analysis was performed to validate PET images.
Safinamide treatment improved behavioral outcomes in stroke-damaged rats. Both [F]SynVesT-1 and [F]FDG PET detected stroke-induced injury, with the injured region being significantly larger in [F]FDG PET than in [F]SynVesT-1 PET. Compared with the saline group, radiotracer uptake in the injured area significantly increased in [F]SynVesT-1 PET after safinamide treatment, whereas no notable change was observed in [F]FDG PET. Additionally, [F]SynVesT-1 PET imaging showed a better correlation with neurological function recovery than [F]FDG PET. Post-mortem analysis revealed increased neuronal numbers, synaptic density, and synaptic neuroplasticity, as well as decreased glia activation in the stroke-injured area after treatment.
[F]SynVesT-1 PET effectively quantified spatiotemporal dynamics of synaptic density in the rat model of stroke, and showed different capabilities in detecting stroke injury and neurological recovery compared with [F]FDG PET. The utilization of [F]SynVesT-1 PET holds promise as a potential non-invasive biomarker for evaluating ischemic stroke in conjunction with [F]FDG PET.
[F]SynVesT-1 是一种用于评估体内突触密度的新型放射性药物。本研究旨在探讨 [F]SynVesT-1 正电子发射断层扫描（PET）在评估缺血性卒中大鼠模型神经功能恢复中的潜力，并将其与 [F]FDG PET 进行比较。
对 Sprague-Dawley 大鼠进行光血栓性脑梗死，术后第 3 天至第 14 天腹腔内给予沙芬酰胺以减轻神经功能缺损。通过圆筒试验和前肢放置试验评估神经功能。MRI、[F]SynVesT-1 PET/CT 和 [F]FDG PET/CT 成像用于评估治疗前后的梗死体积、突触密度和脑葡萄糖代谢。使用统计参数映射（SPM）和感兴趣区（ROI）基于分析比较 [F]SynVesT-1 和 [F]FDG PET 图像。进行死后组织学分析以验证 PET 图像。
沙芬酰胺治疗改善了卒中损伤大鼠的行为学结果。[F]SynVesT-1 和 [F]FDG PET 均检测到卒中引起的损伤，[F]FDG PET 检测到的损伤区域明显大于 [F]SynVesT-1 PET。与盐水组相比，沙芬酰胺治疗后 [F]SynVesT-1 PET 损伤区域的放射性示踪剂摄取显著增加，而 [F]FDG PET 未见明显变化。此外，[F]SynVesT-1 PET 成像与神经功能恢复的相关性优于 [F]FDG PET。死后分析显示，治疗后卒中损伤区域神经元数量、突触密度和突触神经可塑性增加，胶质细胞激活减少。
[F]SynVesT-1 PET 有效量化了卒中大鼠模型中突触密度的时空动态变化，与 [F]FDG PET 相比，在检测卒中损伤和神经功能恢复方面具有不同的能力。[F]SynVesT-1 PET 的应用有望成为评估缺血性卒中的潜在非侵入性生物标志物，与 [F]FDG PET 联合使用。
