The rationale for application of nanotechnology in targeted alpha therapy (TAT) is sound.
However, the translational strategy requires attention. Formulation of TAT in nanoparticulate
drug delivery systems has the potential to resolve many of the issues currently experienced. As
-particle emitters are more cytotoxic compared to beta-minus-emitting agents, the results of poor
biodistribution are more dangerous. Formulation in nanotechnology is also suggested to be the ideal
solution for containing the recoil daughters emitted by actinium-225, radium-223, and thorium-227.
Nanoparticle-based TAT is likely to increase stability, enhance radiation dosimetry profiles, and
increase therapeutic efficacy. Unfortunately, nanoparticles have their own unique barriers towards
clinical translation. A major obstacle is accumulation in critical organs such as the spleen, liver,
and lungs. Furthermore, inflammation, necrosis, reactive oxidative species, and apoptosis are key
mechanisms through which nanoparticle-mediated toxicity takes place. It is important at this stage
of the technology’s readiness level that focus is shifted to clinical translation. The relative scarcity of
-particle emitters also contributes to slow-moving research in the field of TAT nanotechnology. This
review describes approaches and solutions which may overcome obstacles impeding nanoparticlebased
TAT and enhance clinical translation. In addition, an in-depth discussion of relevant issues
and a view on technical and regulatory barriers are presented.