Cutting edge rare earth radiometals: prospects for cancer theranostics

Abstract

Background: 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.

Main body: 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 (¹⁴⁹Tb), β^--therapy (⁴⁷Sc, ¹⁶¹Tb, ¹⁶⁶Ho, ¹⁵³Sm, ¹⁶⁹Er, ¹⁴⁹Pm, ¹⁴³Pr, ¹⁷⁰Tm), Auger electron (AE) therapy (¹⁶¹Tb, ¹³⁵La, ¹⁶⁵Er), positron emission tomography (⁴³Sc, ⁴⁴Sc, ¹⁴⁹Tb, ¹⁵²Tb, ¹³²La, ¹³³La), and single photon emission computed tomography (⁴⁷Sc, ¹⁵⁵Tb, ¹⁵²Tb, ¹⁶¹Tb, ¹⁶⁶Ho, ¹⁵³Sm, ¹⁴⁹Pm, ¹⁷⁰Tm). 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.

Conclusions: 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.

Keywords: Cancer; Imaging; Lanthanoid; Radionuclide production; Rare earth; Theranostics; Therapy.