TY - JOUR
T1 - Improved 225Ac daughter retention in InPO4 containing polymersomes
AU - de Kruijff, R. M.
AU - Drost, K.
AU - Thijssen, L.
AU - Morgenstern, A
AU - Bruchertseifer, F
AU - Lathouwers, D.
AU - Wolterbeek, H. T.
AU - Denkova, A. G.
PY - 2017
Y1 - 2017
N2 - 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, from 37 ± 4% and 22 ± 1% to 57 ± 5% and 40 ± 2% for 221Fr and 213Bi respectively for 100 nm polymersomes, as compared to earlier published results by Wang et al. where 225Ac was encapsulated using a hydrophilic chelate (Wang et al. 2014). 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.
AB - 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, from 37 ± 4% and 22 ± 1% to 57 ± 5% and 40 ± 2% for 221Fr and 213Bi respectively for 100 nm polymersomes, as compared to earlier published results by Wang et al. where 225Ac was encapsulated using a hydrophilic chelate (Wang et al. 2014). 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.
UR - http://www.scopus.com/inward/record.url?scp=85024914497&partnerID=8YFLogxK
U2 - 10.1016/j.apradiso.2017.07.030
DO - 10.1016/j.apradiso.2017.07.030
M3 - Article
AN - SCOPUS:85024914497
SN - 0969-8043
VL - 128
SP - 183
EP - 189
JO - Applied Radiation and Isotopes
JF - Applied Radiation and Isotopes
ER -