Sadler Alexander W E, Hogan Leena, Fraser Benjamin, Rendina Louis M
School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia.
ANSTO Life Sciences, Australian Nuclear Science and Technology Organisation (ANSTO), Kirrawee, NSW, 2232, Australia.
EJNMMI Radiopharm Chem. 2022 Aug 26;7(1):21. doi: 10.1186/s41181-022-00173-0.
With recent advances in novel approaches to cancer therapy and imaging, the application of theranostic techniques in personalised medicine has emerged as a very promising avenue of research inquiry in recent years. Interest has been directed towards the theranostic potential of Rare Earth radiometals due to their closely related chemical properties which allow for their facile and interchangeable incorporation into identical bifunctional chelators or targeting biomolecules for use in a diverse range of cancer imaging and therapeutic applications without additional modification, i.e. a "one-size-fits-all" approach. This review will focus on recent progress and innovations in the area of Rare Earth radionuclides for theranostic applications by providing a detailed snapshot of their current state of production by means of nuclear reactions, subsequent promising theranostic capabilities in the clinic, as well as a discussion of factors that have impacted upon their progress through the theranostic drug development pipeline.
In light of this interest, a great deal of research has also been focussed towards certain under-utilised Rare Earth radionuclides with diverse and favourable decay characteristics which span the broad spectrum of most cancer imaging and therapeutic applications, with potential nuclides suitable for α-therapy (Tb), β-therapy (Sc, Tb, Ho, Sm, Er, Pm, Pr, Tm), Auger electron (AE) therapy (Tb, La, Er), positron emission tomography (Sc, Sc, Tb, Tb, La, La), and single photon emission computed tomography (Sc, Tb, Tb, Tb, Ho, Sm, Pm, Tm). For a number of the aforementioned radionuclides, their progression from 'bench to bedside' has been hamstrung by lack of availability due to production and purification methods requiring further optimisation.
In order to exploit the potential of these radionuclides, reliable and economical production and purification methods that provide the desired radionuclides in high yield and purity are required. With more reactors around the world being decommissioned in future, solutions to radionuclide production issues will likely be found in a greater focus on linear accelerator and cyclotron infrastructure and production methods, as well as mass separation methods. Recent progress towards the optimisation of these and other radionuclide production and purification methods has increased the feasibility of utilising Rare Earth radiometals in both preclinical and clinical settings, thereby placing them at the forefront of radiometals research for cancer theranostics.
随着癌症治疗和成像新方法的最新进展，近年来，治疗诊断技术在个性化医疗中的应用已成为一个非常有前景的研究领域。由于稀土放射性金属具有密切相关的化学性质，人们对其治疗诊断潜力产生了兴趣，这使得它们能够轻松且可互换地掺入相同的双功能螯合剂或靶向生物分子中，用于各种癌症成像和治疗应用，而无需额外修饰，即“一刀切”的方法。本综述将通过详细介绍稀土放射性核素目前通过核反应的生产状态、随后在临床上有前景的治疗诊断能力，以及讨论影响它们在治疗诊断药物开发管道中进展的因素，来关注稀土放射性核素在治疗诊断应用领域的最新进展和创新。
鉴于这种兴趣，大量研究也集中在某些未充分利用的稀土放射性核素上，它们具有多样且有利的衰变特性，涵盖了大多数癌症成像和治疗应用的广泛范围，潜在的核素适用于α治疗（铽）、β治疗（钪、铽、钬、钐、铒、钷、镨、铥）、俄歇电子（AE）治疗（铽、镧、铒）、正电子发射断层扫描（钪、钪、铽、铽、镧、镧）和单光子发射计算机断层扫描（钪、铽、铽、铽、钬、钐、钷、铥）。对于上述许多放射性核素，由于生产和纯化方法需要进一步优化导致缺乏可用性，它们从“实验室到临床”的进展受到了阻碍。
为了开发这些放射性核素的潜力，需要可靠且经济的生产和纯化方法，以高产量和高纯度提供所需的放射性核素。随着未来世界各地更多反应堆退役，放射性核素生产问题的解决方案可能在于更加关注直线加速器和回旋加速器基础设施及生产方法，以及质量分离方法。这些以及其他放射性核素生产和纯化方法优化方面的最新进展增加了在临床前和临床环境中使用稀土放射性金属的可行性，从而使它们处于癌症治疗诊断放射性金属研究的前沿。
