[¹⁸F]SynVesT-1 is a PET radiopharmaceutical that binds to the synaptic vesicle protein 2A (SV2A) and serves as a biomarker of synaptic density with widespread clinical research applications in psychiatry and neurodegeneration. The initial goal of this study was to concurrently conduct PET imaging studies with [¹⁸F]SynVesT-1 at our laboratories. However, the data in the first two human PET studies had anomalous biodistribution despite the injected product meeting all specifications during the prerelease quality control protocols. Further investigation, including imaging in rats as well as proton and carbon 2D-NMR spectroscopic studies, led to the discovery that a derivative of the precursor had been received from the manufacturer. Hence, we report our investigation and the first-in-human study of [¹⁸F]SDM-4MP3, a structural variant of [¹⁸F]SynVesT-1, which does not have the requisite characteristics as a PET radiopharmaceutical for imaging SV2A in the central nervous system.

中文翻译：

---

[18F]SDM-4MP3 的首次人体 PET 成像：一个警示故事

[ ¹⁸ F]SynVesT-1 是一种 PET 放射性药物，可与突触小泡蛋白 2A (SV2A) 结合，并作为突触密度的生物标志物，在精神病学和神经退行性疾病方面具有广泛的临床研究应用。本研究的最初目标是在我们的实验室同时使用 [ ¹⁸ F]SynVesT-1 进行 PET 成像研究。然而，尽管注射产品符合预发布质量控制方案中的所有规格，但前两项人体 PET 研究的数据存在异常生物分布。进一步的研究，包括大鼠成像以及质子和碳 2D-NMR 光谱研究，发现制造商已收到前体的衍生物。^{因此，我们报告了我们对 [ 18} F]SDM-4MP3的调查和首次人体研究，[ ¹⁸ F]SynVesT-1的结构变体，它不具备作为 PET 放射性药物在 SV2A 成像中所必需的特性。中枢神经系统。