Dosimetry in targeted alpha therapy. A systematic review: current findings and what is needed.

Objective . A systematic review of dosimetry in Targeted Alpha Therapy (TAT) has been performed, identifying the common issues. Approach . The systematic review was performed in accordance with the PRISMA guidelines, and the literature was searched using the Scopus and PubMed databases. Main results . From the systematic review, three key points should be considered when performing dosimetry in TAT. (1) Biodistribution/Biokinetics: the accuracy of the biodistribution data is a limit to accurate dosimetry in TAT. The biodistribution of alpha-emitting radionuclides throughout the body is difficult to image directly, with surrogate radionuclide imaging, blood/faecal sampling, and animal studies able to provide information. (2) Daughter radionuclides: the decay energy of the alpha-emissions is sufficient to break the bond to the targeting vector, resulting in a release of free daughter radionuclides in the body. Accounting for daughter radionuclide migration is essential. (3) Small-scale dosimetry and microdosimetry: due to the short path length and heterogeneous distribution of alpha-emitters at the target site, small-scale/microdosimetry are important to account for the non-uniform dose distribution in a target region, organ or cell and for assessing the biological effect of alpha-particle radiation. Significance . TAT is a form of cancer treatment capable of delivering a highly localised dose to the tumour environment while sparing the surrounding healthy tissue. Dosimetry is an important part of treatment planning and follow up. Being able to accurately predict the radiation dose to the target region and healthy organs could guide the optimal prescribed activity. Detailed dosimetry models accounting for the three points mentioned above will help give confidence in and guide the clinical application of alpha-emitting radionuclides in targeted cancer therapy.