First-in-Human PET Imaging of [¹⁸F]SDM-4MP3: A Cautionary Tale.

IF 2.2 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Molecular Imaging Pub Date : 2023-09-08 eCollection Date: 2023-01-01 DOI:10.1155/2023/8826977

Kimberly L Desmond, Anton Lindberg, Armando Garcia, Junchao Tong, Michael B Harkness, Elena Dobrota, Kelly Smart, Carme Uribe, Jeffrey H Meyer, Sylvain Houle, Antonio P Strafella, Songye Li, Yiyun Huang, Neil Vasdev

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引用次数: 1

Abstract

[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.

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[18F]SDM-4MP3的首次人体PET成像：一个警示故事。

[18F]SynVesT-1是一种PET放射性药物，与突触小泡蛋白2A（SV2A）结合，是突触密度的生物标志物，在精神病学和神经退行性变中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进行[18F]SynVesT-1的PET成像研究。然而，前两项人体PET研究中的数据具有异常的生物分布，尽管注射的产品在释放前质量控制方案中符合所有规范。进一步的研究，包括在大鼠中成像以及质子和碳2D-NMR光谱研究，发现从制造商那里收到了前体的衍生物。因此，我们报告了我们对[18F]SDM-4MP3的研究，这是[18F]SynVesT-1的一种结构变体，它不具有作为中枢神经系统SV2A成像的PET放射性药物的必要特征。

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来源期刊

Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology

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3.60%

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期刊介绍： Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.