Abstract
BackgroundActinium-225 is an alpha-particle emitter under investigation for use in radiopharmaceutical therapy. To address limited supply, accelerator-produced 225Ac has been recently made available. Accelerator-produced 225Ac via 232Th irradiation (denoted 225/7Ac) contains a low percentage (0.1–0.3%) of 227Ac (21.77-year half-life) activity at end of bombardment. Using pharmacokinetic modeling, we have examined the dosimetric impact of 227Ac on the use of accelerator-produced 225Ac for radiopharmaceutical therapy. We examine the contribution of 227Ac and its daughters to tissue absorbed doses. The dosimetric analysis was performed for antibody-conjugated 225/7Ac administered intravenously to treat patients with hematological cancers. Published pharmacokinetic models are used to obtain the distribution of 225/7Ac-labeled antibody and also the distribution of either free or antibody-conjugated 227Th.ResultsBased on our modeling, the tissue specific absorbed dose from 227Ac would be negligible in the context of therapy, less than 0.02 mGy/MBq for the top 6 highest absorbed tissues and less than 0.007 mGy/MBq for all other tissues. Compared to that from 225Ac, the absorbed dose from 227Ac makes up a very small component (less than 0.04%) of the total absorbed dose delivered to the 6 highest dose tissues: red marrow, spleen, endosteal cells, liver, lungs and kidneys when accelerator produced 225/7Ac-conjugated anti-CD33 antibody is used to treat leukemia patients. For all tissues, the dominant contributor to the absorbed dose arising from the 227Ac is 227Th, the first daughter of 227Ac which has the potential to deliver absorbed dose both while it is antibody-bound and while it is free. CONCLUSIONS: These results suggest that the absorbed dose arising from 227Ac to normal organs would be negligible for an 225/7Ac-labeled antibody that targets hematological cancer.
Highlights
Alpha-particle emitter radiopharmaceutical therapy is a promising new approach to cancer therapy
We have examined the dosimetric impact of 227Ac on the use of accelerator-produced 225Ac for radiopharmaceutical therapy
Compared to that from 225Ac, the absorbed dose from 227Ac makes up a very small component of the total absorbed dose delivered to the 6 highest dose tissues: red marrow, spleen, endosteal cells, liver, lungs and kidneys when accelerator produced 225/7Ac-conjugated anti-CD33 antibody is used to treat leukemia patients
Summary
Alpha-particle emitter radiopharmaceutical therapy (αRPT) is a promising new approach to cancer therapy. Current limitation of available 225Ac supply, due to the fixed output from 229Th generator, has been a concern that has impacted preclinical and clinical use of 225Ac-based αRPT [4]. Accelerator-produced 225Ac via 232Th irradiation (hereafter denoted as 225/7Ac) contains 0.1 to 0.3% 227Ac (21.77-year half-life) activity at end of bombardment [8]. To account for the time elapsed for processing, transport and injectate preparation, we consider a scenario where the injected, 225/7Ac radiolabeled conjugate contains 0.7% 227Ac. Actinium-225 is an alpha-particle emitter under investigation for use in radiopharmaceutical therapy. Accelerator-produced 225Ac via 232Th irradiation (denoted 225/7Ac) contains a low percentage (0.1–0.3%) of 227Ac (21.77-year half-life) activity at end of bombardment. We have examined the dosimetric impact of 227Ac on the use of accelerator-produced 225Ac for radiopharmaceutical therapy. Published pharmacokinetic models are used to obtain the distribution of 225/7Ac-labeled antibody and the distribution of either free or antibody-conjugated 227Th
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