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Sci Rep. 2019 Aug 12;9(1):11671. doi: 10.1038/s41598-019-48298-8.

The in vivo fate of 225Ac daughter nuclides using polymersomes as a model carrier.

Author information

1
Radiation Science and Technology, Delft University of Technology, Delft, The Netherlands. r.m.dekruijff@tudelft.nl.
2
Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, The Netherlands.
3
European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany.
4
Radiation Science and Technology, Delft University of Technology, Delft, The Netherlands.

Abstract

Increasing attention is given to personalized tumour therapy, where α-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 α 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 225Ac in vivo, and assessed their suitability as therapeutic agents. Vesicles containing 225Ac were injected intravenously in healthy mice, and intratumourally in tumour-bearing mice, and the relocation of free 213Bi was assessed in different organs upon the injection [225Ac]Ac-polymersomes. The therapeutic effect of 225Ac-containing vesicles was studied upon intratumoural injection, where treatment groups experienced no tumour-related deaths over a 115 day period. While polymersomes containing 225Ac 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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