A comparative evaluation of Ac225 vs Bi213 as therapeutic radioisotopes for targeted alpha therapy for cancer
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The Ac225:Bi213 generator is the mainstay for preclinical and clinical studies of targeted alpha therapy for cancer. Both Ac225 (four alpha decays) and Bi213 (one alpha decay) are being used to label targeting vectors to form the alpha immunoconjugate for cancer therapy. This paper considers the radiobiological and economic aspects of Ac225 vs Bi213 as the preferred radioisotope for preclinical and clinical TAT. The in vitro and in vivo evidence and the role of DNA repair processes is examined. The maximum tolerance dose and therapeutic gain are endpoints for comparison. Ac225 has the higher therapeutic gain, when normalised to equal alpha production. However, the slow repair of double strand breaks reduces this advantage. Comparisons are made for the specific energy deposition in targeted and non-targeted cells, for endothelial cells by direct or indirect targeting, the need for sparing agents to save critical organs and cost considerations for preclinical and clinical trials and clinical use. Overall, Ac225 is found to have the better or equal performance to Bi213 at a much lower cost.
KeywordsTargeted alpha therapy Cancer Therapeutic radioisotopes Bi213 Ac225 DSB repair Cell survival Specific activity Anti-vascular therapy Maximum tolerance dose
My thanks for e-discussions with George Sgouros and Alfred Morgenstern.
Compliance with ethical standards
Conflict of interest
The author declares that he has no conflict of interest.
There are neither animal nor human experiments in this publication.
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