The in vivo fate of (225)Ac daughter nuclides using polymersomes as a model carrier
SourceScientific Reports, 9, (2019), article 11671
Article / Letter to editor
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SubjectRadboudumc 14: Tumours of the digestive tract RIHS: Radboud Institute for Health Sciences; Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences
Increasing attention is given to personalized tumour therapy, where alpha-emitters can potentially play an important role. Alpha particles are ideal for localized cell killing because of their high linear energy transfer and short ranges. However, upon the emission of an alpha particle the daughter nuclide experiences a recoil energy large enough to ensure decoupling from any chemical bond. These 'free' daughter nuclides are no longer targeted to the tumour and can accumulate in normal tissue. In this paper, we used polymersomes as model carrier to evaluate the retention of recoiling daughters of (225)Ac in vivo, and assessed their suitability as therapeutic agents. Vesicles containing (225)Ac were injected intravenously in healthy mice, and intratumourally in tumour-bearing mice, and the relocation of free (213)Bi was assessed in different organs upon the injection [(225)Ac]Ac-polymersomes. The therapeutic effect of (225)Ac-containing vesicles was studied upon intratumoural injection, where treatment groups experienced no tumour-related deaths over a 115 day period. While polymersomes containing (225)Ac could be suitable agents for long-term irradiation of tumours without causing significant renal toxicity, there is still a significant re-distribution of daughter nuclides throughout the body, signifying the importance of careful evaluation of the effect of daughter nuclides in targeted alpha therapy.
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