TY - JOUR
T1 - An investigation of calcium carbonate core-shell particles for incorporation of 225Ac and sequester of daughter radionuclides
T2 - in vitro and in vivo studies
AU - Muslimov, Albert R.
AU - Antuganov, Dmitrii
AU - Tarakanchikova, Yana V.
AU - Karpov, Timofey E.
AU - Zhukov, Mikhail V.
AU - Zyuzin, Mikhail V.
AU - Timin, Alexander S.
N1 - Funding Information:
This work was performed with financial support of the Russian Science Foundation (project No. 19-75-10010 ). The part of this work regarding interaction of the developed particles with biological systems was supported with the Russian Science Foundation (project No. 19-75-00039 ). The research is funded from Tomsk Polytechnic University Competitiveness Enhancement Program.
Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/10
Y1 - 2021/2/10
N2 - Alpha therapy provides an outstanding prospect in the treatment of recalcitrant and micrometastatic cancers. However, side effects on the normal tissues and organs (especially, kidneys) due to the release of daughter isotopes from α-emitters remain a bottleneck. In this work, calcium carbonate core-shell particles of different sizes were considered as isotope carriers for encapsulation of 225Ac (highly powerful alpha-emitter that generates 4 net alpha particle isotopes in a short decay chain) in order to achieve in vitro and in vivo retention of 225Ac and its daughter isotopes. According to the in vitro studies, the developed calcium carbonate core-shell particles were able to retain 225Ac and its daughter isotopes (221Fr and 213Bi) exhibited good stability in biological media and dose-dependent biocompatibility (over 30 d). The SPECT imaging demonstrated the size-dependent distribution of 225Ac-doped core-shell particles. Further, in vivo studies confirmed the high retention efficiency of calcium carbonate core-shell particles, which was demonstrated in normal Wistar rats (up to 10 d). Interestingly, the radioactivity accumulation in kidney and urine was significantly less for encapsulated 225Ac than in case of non-encapsulated form of 225Ac (225Ac conjugated with albumin), indicating the absence of radioisotope leakage from the developed particles. Thus, our study validates the application of 225Ac-doped core-shell particles to sequester α-emitter (225Ac) and its decay products in order to reduce their systemic toxicity during alpha therapy.
AB - Alpha therapy provides an outstanding prospect in the treatment of recalcitrant and micrometastatic cancers. However, side effects on the normal tissues and organs (especially, kidneys) due to the release of daughter isotopes from α-emitters remain a bottleneck. In this work, calcium carbonate core-shell particles of different sizes were considered as isotope carriers for encapsulation of 225Ac (highly powerful alpha-emitter that generates 4 net alpha particle isotopes in a short decay chain) in order to achieve in vitro and in vivo retention of 225Ac and its daughter isotopes. According to the in vitro studies, the developed calcium carbonate core-shell particles were able to retain 225Ac and its daughter isotopes (221Fr and 213Bi) exhibited good stability in biological media and dose-dependent biocompatibility (over 30 d). The SPECT imaging demonstrated the size-dependent distribution of 225Ac-doped core-shell particles. Further, in vivo studies confirmed the high retention efficiency of calcium carbonate core-shell particles, which was demonstrated in normal Wistar rats (up to 10 d). Interestingly, the radioactivity accumulation in kidney and urine was significantly less for encapsulated 225Ac than in case of non-encapsulated form of 225Ac (225Ac conjugated with albumin), indicating the absence of radioisotope leakage from the developed particles. Thus, our study validates the application of 225Ac-doped core-shell particles to sequester α-emitter (225Ac) and its decay products in order to reduce their systemic toxicity during alpha therapy.
KW - Actinium
KW - Alpha therapy
KW - Calcium carbonate
KW - Core-shell particles
KW - Daughter isotopes
KW - in vivo biodistribution
KW - Radiolabeling
KW - Radionuclide retention
KW - SPECT
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U2 - 10.1016/j.jconrel.2021.01.008
DO - 10.1016/j.jconrel.2021.01.008
M3 - Article
AN - SCOPUS:85099387775
VL - 330
SP - 726
EP - 737
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -