Targeted Alpha-Particle Therapy: A Review of Current Trials

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters ((225)actinium, (212)lead, and (211)astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.

Automated summary

Radiopharmaceuticals are rapidly developing as a field, with targeted beta and alpha emitters being investigated for oncologic indications. Clinical trials are currently underway for conjugated/chelated alpha emitters, with multiple diseases being targeted in phase I trials and a phase III trial in neuroendocrine cancers. Challenges remain in terms of supply chains, understanding administered dose and absorbed dose relationships, and potential long-term effects of alpha emitters.