Brühlmann Santiago Andrés, Walther Martin, Kopka Klaus, Kreller Martin
Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01062, Dresden, Germany.
EJNMMI Radiopharm Chem. 2024 Jan 5;9(1):3. doi: 10.1186/s41181-023-00233-z.
There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio Cu, Cu and Cu, 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 Cu, 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 Cu may as well be beneficial.
Proton irradiation of enriched Ni electrodeposited targets with a compact cyclotron produced the desired radionuclide via the Ni(p,2n)Cu nuclear reaction, leading to Cu 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 [Cu]CuCl 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.
In the current article a comprehensive novel production method for the PET radionuclide Cu is presented, providing an alternative to the most popular production routes. Characterization of the [Cu]CuCl 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.
真正的诊疗一体化匹配对很少,特别是分别用于诊断和治疗的诊疗一体化放射性铜三元组Cu、Cu和Cu,是一个非常有吸引力的候选方案。事实上,两种具有不同半衰期的成像放射性核素的组合相对于其他诊疗一体化对具有明显优势,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Cu的可用性高,其临床转化正在成功进行,例如美国食品药品监督管理局(FDA)批准的放射性药物Detectnet(铜Cu 64多他胺注射液)。然而,像Cu这样半衰期较短的正电子发射断层扫描(PET)放射性核素可能也有益处。
用紧凑型回旋加速器对富集的镍电沉积靶进行质子辐照,通过Ni(p,2n)Cu核反应产生了所需的放射性核素,轰击结束时Cu活度高达20 GBq,纯化结束时为8 GBq。此外,比较了两种纯化方法,在分离产率和产品纯度方面得到了可比的结果。放射性化学分离后,对该产品[Cu]CuCl溶液的质量评估证明,使用1,4,8,11 - 四氮杂环十四烷 - 1,4,8,11 - 四乙酸(TETA)螯合剂时,纯化结束校正后的放射性核素纯度(RNP)超过99.6%,表观摩尔活度(AMA)为260 GBq/µmol。
在本文中,提出了一种用于PET放射性核素Cu的全面新颖的生产方法,为最常用的生产路线提供了替代方案。[Cu]CuCl产品的表征显示出高RNP和高AMA,证明所产生的活度在纯化结束后长达9小时的放射性标记方面具有高质量。此外,通过增加辐照时间可以轻松实现生产规模扩大。