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.

Rare Earths—The Answer to Everything

“…Mixed metal oxides have the advantage over mixed metal complexes of a higher load of the requisite metals. This much to be desired combination of imaging and treatment is termed Cancer Theranostics, and it has been the subject of three substantial recent reviews [162][163][164]. The former review considers in detail the radiochemical advantages and disadvantages of a whole range of accessible isotopes to provide a basis for the choice of imaging and scanning options.…”

“…Particularly, the authors cover the route for the relevant isotope production and the isotopic properties. A highly desirable situation is where different isotopes of the same element can perform different functions, as this simplifies the chemistry and biochemistry involved [162]. The second is focused more on clinical outcomes and rare earth compounds are considered only as part of a much wider range of radiochemical reagents [163].…”

High Separation Factor, High Molar Activity, and Inexpensive Purification Method for the Production of Pure 165Er

“…10 Radio lanthanides are easily chelated, form theranostic pairs with actinides, and contain several interesting radionuclides for TRT. 11 One reason for the popularity of radiolenthanides is that they can be easily chelated. Also, their similar chemical properties allow for the use of identical targeting vectors and bifunctional chelators to label these metals with little to no modification.…”

“…Radio lanthanides have gained popularity in recent years as potential candidates for both diagnosis and treatment of cancer . Radio lanthanides are easily chelated, form theranostic pairs with actinides, and contain several interesting radionuclides for TRT . One reason for the popularity of radiolenthanides is that they can be easily chelated.…”

Effect of Gd3+, La3+, Lu3+ Co-Doping on the Morphology and Luminescent Properties of NaYF4:Sm3+ Phosphors

“…Samarium compounds are of interest in medicine and the production of functional nanoparticles. For example, the decay energy of the samarium 153 Sm nuclide allows using this isotope for cancer therapy and SPECT imaging [ 32 , 33 ]. Sm 3+ ions are also known to be used as a part of optically active materials because of their orange luminescence, originating from the 4 G 5/2 → 6 H J/2 (J = 5, 7, and 9) transitions [ 14 , 34 , 35 , 36 , 37 ].…”