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- W3196268644 abstract "Abstract Background Actinium-225 is an alpha-particle emitter under investigation for use in radiopharmaceutical therapy. To address limited supply, accelerator-produced 225 Ac has been recently made available. Accelerator-produced 225 Ac via 232 Th irradiation (denoted 225/7 Ac) contains a low percentage (0.1–0.3%) of 227 Ac (21.77-year half-life) activity at end of bombardment. Using pharmacokinetic modeling, we have examined the dosimetric impact of 227 Ac on the use of accelerator-produced 225 Ac for radiopharmaceutical therapy. We examine the contribution of 227 Ac and its daughters to tissue absorbed doses. The dosimetric analysis was performed for antibody-conjugated 225/7 Ac administered intravenously to treat patients with hematological cancers. Published pharmacokinetic models are used to obtain the distribution of 225/7 Ac-labeled antibody and also the distribution of either free or antibody-conjugated 227 Th. Results Based on our modeling, the tissue specific absorbed dose from 227 Ac 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 225 Ac, the absorbed dose from 227 Ac 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 225/7 Ac-conjugated anti-CD33 antibody is used to treat leukemia patients. For all tissues, the dominant contributor to the absorbed dose arising from the 227 Ac is 227 Th, the first daughter of 227 Ac 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 227 Ac to normal organs would be negligible for an 225/7 Ac-labeled antibody that targets hematological cancer." @default.
- W3196268644 created "2021-08-30" @default.
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- W3196268644 date "2021-08-18" @default.
- W3196268644 modified "2023-10-15" @default.
- W3196268644 title "Dosimetric impact of Ac-227 in accelerator-produced Ac-225 for alpha-emitter radiopharmaceutical therapy of patients with hematological malignancies: a pharmacokinetic modeling analysis" @default.
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- W3196268644 doi "https://doi.org/10.1186/s40658-021-00410-6" @default.
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