Meier Jason P, Bhuiyan Mohammed, Freifelder Richard, Zhang Hannah J, Gonzalez Lucas, Pusateri Antonino, Tsai Hsiu-Ming, Leoni Lara, Ghosh Kaustab, Markiewicz Erica, Henning Christopher, Zhang Yuhan, Weichselbaum Ralph, Nolen Jerry, Rotsch David A, Kao Chien-Min, Szmulewitz Russell Z, Chen Chin-Tu, Chitneni Satish K
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA.
Cyclotron Facility, The University of Chicago, Chicago, IL 60637, USA.
Methods Protoc. 2025 Jun 4;8(3):58. doi: 10.3390/mps8030058.
The implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [Ga]Ga-PSMA-11 PET and [Lu]Lu-PSMA-617 into clinical practice. However, the correlation between radiopharmaceutical biodistributions seen with [Ga]Ga-PSMA-11 PET imaging and downstream [Lu]Lu-PSMA-617 therapy remains imperfect. This suggests that prostate cancer theranostics could potentially be further refined through the implementation of true theranostics, tandem pairs of diagnostic and therapeutic radiopharmaceuticals that utilize the same ligand and element, thus yielding identical pharmacokinetics. The radioscandiums are one such group of true theranostic radiopharmaceuticals. The radioscandiums consist of two β+ emitting scandium isotopes (Sc/Sc), as well as a β emitting therapeutic isotope (Sc), which can all conjugate with PSMA-targeting PSMA-617. This potential has led to extensive investigations into the production of the radioscandiums as well as pre-clinical assessments with several ligands; however, there is a lack of literature extensively describing the complete synthesis of scandium radiopharmaceuticals. which therefore limits the accessibility of radioscandium research in theranostics. As such, this work aims to present an easily translatable protocol for the synthesis of [Sc]Sc-PSMA-617 from a [Ca]CaCO starting material, including target formation, nuclear production via Ca(d,n)Sc reaction, chemical separation, radiolabeling, solvent reformulation, and target recycling.
在肿瘤核医学中，通过将[镓]Ga-PSMA-11 PET和[镥]Lu-PSMA-617应用于临床实践，治疗诊断学在改善前列腺癌患者预后方面展现出了巨大潜力。然而，[镓]Ga-PSMA-11 PET成像所见放射性药物生物分布与下游[镥]Lu-PSMA-617治疗之间的相关性仍不完善。这表明，通过实施真正的治疗诊断学，即利用相同配体和元素的诊断与治疗放射性药物串联对，从而产生相同的药代动力学，前列腺癌治疗诊断学可能会得到进一步优化。放射性钪就是这样一类真正的治疗诊断放射性药物。放射性钪由两种发射β+的钪同位素（Sc/Sc）以及一种发射β的治疗性同位素（Sc）组成，它们都可以与靶向PSMA的PSMA-617共轭。这种潜力引发了对放射性钪生产以及使用多种配体进行临床前评估的广泛研究；然而，缺乏广泛描述钪放射性药物完整合成过程的文献。这因此限制了治疗诊断学中放射性钪研究的可及性。因此，这项工作旨在展示一种易于转化的方案，用于从[钙]CaCO起始原料合成[钪]Sc-PSMA-617，包括靶标形成、通过Ca(d,n)Sc反应进行核生产、化学分离、放射性标记、溶剂重新配制以及靶标回收。
