Fonseca Alexandra I, Alves Vítor H, do Carmo Sérgio J C, Silva Magda, Hrynchak Ivanna, Alves Francisco, Falcão Amílcar, Abrunhosa Antero J
ICNAS Produção Unipessoal, Lda., Ed. ICNAS, Polo das Ciências da Saúde, University of Coimbra, 3000-548 Coimbra, Portugal.
Fluidomica, Lda., 3060-197 Cantanhede, Portugal.
Pharmaceuticals (Basel). 2022 Jun 7;15(6):723. doi: 10.3390/ph15060723.
PET imaging has gained significant momentum in the last few years, especially in the area of oncology, with an increasing focus on metal radioisotopes owing to their versatile chemistry and favourable physical properties. Copper-61 (t = 3.33 h, 61% β, E = 1.216 MeV) provides unique advantages versus the current clinical standard (i.e., gallium-68) even though, until now, no clinical amounts of Cu-based radiopharmaceuticals, other than thiosemicarbazone-based molecules, have been produced. This study aimed to establish a routine production, using a standard medical cyclotron, for a series of widely used somatostatin analogues, currently labelled with gallium-68, that could benefit from the improved characteristics of copper-61. We describe two possible routes to produce the radiopharmaceutical precursor, either from natural zinc or enriched zinc-64 liquid targets and further synthesis of [Cu]Cu-DOTA-NOC, [Cu]Cu-DOTA-TOC and [Cu]Cu-DOTA-TATE with a fully automated GMP-compliant process. The production from enriched targets leads to twice the amount of activity (3.28 ± 0.41 GBq vs. 1.84 ± 0.24 GBq at EOB) and higher radionuclidic purity (99.97% vs. 98.49% at EOB). Our results demonstrate, for the first time, that clinical doses of Cu-based radiopharmaceuticals can easily be obtained in centres with a typical biomedical cyclotron optimised to produce F-based radiopharmaceuticals.
在过去几年中，正电子发射断层扫描（PET）成像发展迅猛，尤其是在肿瘤学领域。由于金属放射性同位素具有多样的化学性质和良好的物理特性，人们对其关注度日益增加。铜 - 61（半衰期t = 3.33小时，61%为β衰变，能量E = 1.216兆电子伏特）与当前临床标准（即镓 - 68）相比具有独特优势，尽管到目前为止，除了基于硫代氨基脲的分子外，尚未生产出临床用量的铜基放射性药物。本研究旨在利用标准医用回旋加速器，为一系列目前用镓 - 68标记的广泛使用的生长抑素类似物建立常规生产方法，这些类似物可受益于铜 - 61改善后的特性。我们描述了两种生产放射性药物前体的可能途径，即从天然锌或富集的锌 - 64液态靶材开始，然后通过完全符合药品生产质量管理规范（GMP）的自动化过程进一步合成[铜 - 61]Cu - DOTA - NOC、[铜 - 61]Cu - DOTA - TOC和[铜 - 61]Cu - DOTA - TATE。使用富集靶材生产可使活度提高两倍（放化结束时为3.28 ± 0.41吉贝可，而天然锌靶材为1.84 ± 0.24吉贝可），并且放射性核素纯度更高（放化结束时为99.97%，而天然锌靶材为98.49%）。我们的结果首次表明，在配备典型生物医学回旋加速器且已优化用于生产氟基放射性药物的中心，能够轻松获得临床剂量的铜基放射性药物。
