Production of [¹⁸F]NAV4694 on an FX2N synthesis module for imaging amyloid plaques.

IF 1.8 3区工程技术 Q3 CHEMISTRY, INORGANIC & NUCLEAR

Applied Radiation and Isotopes Pub Date : 2025-09-30 DOI:10.1016/j.apradiso.2025.112216

Pardeep Kumar, Sandhya Mangalore, Raman Kumar Joshi, Venkatesh Murthy, Aishwarya Kumar, Keerti Sitani, Anupama Vajjala, Yashwanth Gurushanthappa, Deeksha Muralidharan, Manoj Kumar, Palanimuthu T Sivakumar

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引用次数: 0

Abstract

Introduction: Amyloid PET imaging has changed the management of Alzheimer's disease patients. Several radiopharmaceuticals have evolved in the last two decades. We are reporting the synthesis of the amyloid imaging PET tracer fluorine-18[¹⁸F]NAV4694 in the FX2N synthesis module under GMP-compliant conditions for clinical use.

Methods: The radiosynthesis was standardised in the FX2N synthesis module, and the precursor concentration was varied from 0.5 to 2.0 mg for labelling with ¹⁸F at 110 °C, with a reaction time of 5-10 min, followed by hydrolysis with 0.6 M HCl for 5 min. The final purification was standardised with various C18 cartridges to get the maximum yield. All standard quality controls were performed, along with in vivo stability. Briefly, 350 ± 50 MBq of the [¹⁸F]NAV4694 was injected intravenously in patients, and PET-MR imaging was performed. The images were processed, and the distribution of the tracer was visually observed in the brain.

Results: A minimum of 2 mg concentration was found to be suitable for radiolabeling at 110 °C for 10 min and purified via C18 plus long cartridge, providing the highest radiochemical yield of 13 ± 3 % (decay corrected). The radiochemical purity was 99 ± 0.5 % with a molar activity of 255 ± 125 GBq/μmol. The retention time of the [¹⁸F]NAV4694 was 17.6 ± 0.8 min, which was consistent with the UV/Vis peak of cold NAV4694 at 17.4 ± 0.7 min. The residual solvents, like DMSO and ethanol, were less than the prescribed limit. The HPLC (from plasma) showed no primary metabolites in the plasma, and the stability was 96 ± 2 % (in vitro) and 94 ± 2 % (in vivo). The human biodistribution showed a rapid clearance from the blood. The visual analysis showed uptake in cortical grey matter in a positive amyloid scan and in white matter in an amyloid-negative scan.

Conclusion: [¹⁸F]NAV4694 was successfully synthesised in the FX2N synthesis module with high radiochemical purity. It showed distinctive uptake patterns in amyloid-positive and negative scans.

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淀粉样斑块成像FX2N合成模块制备[18F]NAV4694

淀粉样蛋白PET成像改变了阿尔茨海默病患者的管理。在过去的二十年里，有几种放射性药物得到了发展。我们报道在符合gmp的条件下，在FX2N合成模块中合成淀粉样蛋白成像PET示踪剂氟-18[18F]NAV4694用于临床应用。方法：在FX2N合成模块中标准化放射合成，前体浓度0.5 ~ 2.0 mg，用18F在110℃下标记，反应时间5 ~ 10 min，然后用0.6 M HCl水解5 min。最后用各种C18滤芯进行标准化纯化，以获得最大收率。进行了所有标准质量控制，以及体内稳定性。简单地说，患者静脉注射350±50 MBq的[18F]NAV4694，并进行PET-MR成像。对图像进行处理，目视观察示踪剂在脑内的分布。结果：发现最低浓度为2mg适合在110°C下进行10分钟的放射性标记，并通过C18 +长筒纯化，提供最高的放射化学收率为13±3%（衰变校正）。放射化学纯度为99±0.5%，摩尔活性为255±125 GBq/μmol。[18F] na4694的停留时间为17.6±0.8 min，与低温na4694的UV/Vis峰（17.4±0.7 min）一致。DMSO、乙醇等溶剂残留量均小于规定限量。HPLC（来自血浆）显示血浆中无初级代谢物，体外稳定性为96±2%，体内稳定性为94±2%。人体生物分布显示它能迅速从血液中清除。目视分析显示淀粉样蛋白扫描呈阳性时皮质灰质摄取，淀粉样蛋白扫描呈阴性时白质摄取。结论：在FX2N合成模块中成功合成了[18F]NAV4694，具有较高的放射化学纯度。在淀粉样蛋白阳性和阴性扫描中表现出独特的摄取模式。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Applied Radiation and Isotopes 工程技术-核科学技术

CiteScore

3.00

自引率

12.50%

发文量

406

审稿时长

13.5 months

期刊介绍： Applied Radiation and Isotopes provides a high quality medium for the publication of substantial, original and scientific and technological papers on the development and peaceful application of nuclear, radiation and radionuclide techniques in chemistry, physics, biochemistry, biology, medicine, security, engineering and in the earth, planetary and environmental sciences, all including dosimetry. Nuclear techniques are defined in the broadest sense and both experimental and theoretical papers are welcome. They include the development and use of α- and β-particles, X-rays and γ-rays, neutrons and other nuclear particles and radiations from all sources, including radionuclides, synchrotron sources, cyclotrons and reactors and from the natural environment. The journal aims to publish papers with significance to an international audience, containing substantial novelty and scientific impact. The Editors reserve the rights to reject, with or without external review, papers that do not meet these criteria. Papers dealing with radiation processing, i.e., where radiation is used to bring about a biological, chemical or physical change in a material, should be directed to our sister journal Radiation Physics and Chemistry.