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Improved 225Ac daughter retention in InPO4 containing polymersomes

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Alpha-emitting radionuclides like actinium-225 (225Ac) are ideal candidates for the treatment of small metastasised tumours, where the long half-life of 225Ac enables it to also reach less accessible tumours. The main challenge lies in retaining the recoiled alpha-emitting daughter nuclides, which are decoupled from targeting agents upon emission of an alpha particle and can subsequently cause unwanted toxicity to healthy tissue. Polymersomes, vesicles composed of amphiphilic block copolymers, are capable of transporting (radio)pharmaceuticals to tumours, and are ideal candidates for the retention of these daughter nuclides. In this study, the Geant4 Monte Carlo simulation package was used to simulate ideal vesicle designs. Vesicles containing an InPO4 nanoparticle in the core were found to have the highest recoil retention, and were subsequently synthesized in the lab. The recoil retention of two of the daughter nuclides, namely francium-221 (221Fr) and bismuth-213 (213Bi) was determined at different vesicle sizes. Recoil retention was found to have improved significantly as compared to earlier published results by Wang et al. where 225Ac was encapsulated using a hydrophilic chelate. To better understand the different parameters influencing daughter retention, simulation data was expanded to include vesicle polydispersity and nanoparticle position within the polymersome. The high retention of the recoiling daughters and the 225Ac itself makes this vesicle design very suitable for future in vivo verification.
2017-08-01
PERGAMON-ELSEVIER SCIENCE LTD
JRC103932
0969-8043,   
https://publications.jrc.ec.europa.eu/repository/handle/JRC103932,   
10.1016/j.apradiso.2017.07.030,   
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