通过 62Ni(p,2n)61Cu 核反应生产 PET 放射性核素 61Cu。

IF 4.4 Q1 CHEMISTRY, INORGANIC & NUCLEAR EJNMMI Radiopharmacy and Chemistry Pub Date : 2024-01-05 DOI:10.1186/s41181-023-00233-z

Santiago Andrés Brühlmann, Martin Walther, Klaus Kopka, Martin Kreller

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引用次数: 0

摘要

背景：真正匹配的治疗用放射性核素对屈指可数，尤其是 61Cu、64Cu 和 67Cu 三种分别用于诊断和治疗的治疗用放射性铜，是非常有吸引力的候选物质。事实上，使用两种不同半衰期的成像放射性核素比使用其他治疗剂对具有明显的优势，因为它能更好地匹配示踪剂的生物半衰期和放射性核素的物理半衰期。由于 64Cu 的可用性很高，目前已成功将其应用于临床，例如美国食品及药物管理局批准的放射性药物 Detectnet（铜铜 64 dotatate 注射液）。不过，61Cu 等寿命较短的 PET 放射性核素也可能有益：结果：用紧凑型回旋加速器对富集的 62Ni 电沉积靶进行质子辐照，通过 62Ni(p,2n)61Cu 核反应产生了所需的放射性核素，从而在轰击结束时产生了高达 20 GBq 的 61Cu 放射性活度，在纯化结束时产生了 8 GBq 的 61Cu 放射性活度。此外，还对两种纯化方法进行了比较，结果在分离率和产品纯度方面不相上下。在放射化学分离之后，对[61Cu]CuCl2 溶液的质量评估证明，该产品的放射性核素纯度（RNP）超过 99.6%，表观摩尔活度（AMA）为 260 GBq/µmol，使用的螯合剂为 1,4,8,11-四氮杂环十四烷-1,4,8,11-四乙酸（TETA），纯化结束时进行了校正：本文介绍了 PET 放射性核素 61Cu 的综合新型生产方法，为最常用的生产路线提供了一种替代方案。对[61Cu]CuCl2 产物的表征显示了高 RNP 和高 AMA，证明所生产的活性物质在纯化结束后 9 小时内仍具有高质量的放射性标记。此外，通过增加辐照时间，还可以轻松实现生产的可扩展性。

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Production of the PET radionuclide 61Cu via the 62Ni(p,2n)61Cu nuclear reaction

Background

There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio ⁶¹Cu, ⁶⁴Cu and ⁶⁷Cu, for diagnosis and therapy respectively, is a very attractive candidate. In fact, the alternative of two imaging radionuclides with different half-lives is a clear advantage over other theranostic pairs, since it offers a better matching for the tracer biological and radionuclide physical half-lives. Due to the high availability of ⁶⁴Cu, its translation into the clinic is being successfully carried out, giving the example of the FDA approved radiopharmaceutical Detectnet (copper Cu 64 dotatate injection). However, a shorter-lived PET radionuclide such as ⁶¹Cu may as well be beneficial.

Results

Proton irradiation of enriched ⁶²Ni electrodeposited targets with a compact cyclotron produced the desired radionuclide via the ⁶²Ni(p,2n)⁶¹Cu nuclear reaction, leading to ⁶¹Cu activities of up to 20 GBq at end of bombardment and 8 GBq at end of purification. Furthermore, two purification methods are compared leading to comparable results regarding separation yield and product purity. Following the radiochemical separation, quality assessment of this product [⁶¹Cu]CuCl₂ solution proved radionuclidic purities (RNP) over 99.6% and apparent molar activities (AMA) of 260 GBq/µmol with the 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA) chelator, end of purification corrected.

Conclusions

In the current article a comprehensive novel production method for the PET radionuclide ⁶¹Cu is presented, providing an alternative to the most popular production routes. Characterization of the [⁶¹Cu]CuCl₂ product showed both high RNP as well as high AMA, proving that the produced activity presented high quality regarding radiolabeling up to 9 h after end of purification. Furthermore, production scalability could be easily achieved by increasing the irradiation time.