Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for223 Ra and225 Ra for targeted alpha therapy

Abstract Introduction Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as223 Ra,225 Ra, and225 Ac, are of special interest for radiotherapeutic applications as they emit mul...

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Published in:Nuclear medicine and biology 2015, Vol.42 (7), p.614-620
Main Authors: Rojas, J.V, Woodward, J.D, Chen, N, Rondinone, A.J, Castano, C.H, Mirzadeh, S
Format: Article
Language:English
Subjects:
Radiology
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Summary:Abstract Introduction Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as223 Ra,225 Ra, and225 Ac, are of special interest for radiotherapeutic applications as they emit multiple α-particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. In this work, LaPO4 core and core + 2 shells nanoparticles (NPs) (NPs with 2 layers of cold LaPO4 deposited on the core surfaces) were synthesized containing either223 Ra or225 Ra/225 Ac, and the retention of the parents and daughters within the NPs in vitro was investigated. Methods Core LaPO4 NPs were synthesized in aqueous solution by reacting 1 equivalent of La(NO3 )3 , along with few microcuries of either223 Ra or225 Ra/225 Ac, with 1 equivalent of sodium tripolyphosphate (TPP) under moderate heating and purified by membrane dialysis. Core-shell NPs were also synthesized with one (core + 1 shell) and two (core + 2 shells) cold LaPO4 layers deposited onto the radioactive cores. The NPs were then characterized by transmission electron microscopy (TEM) and powder x-ray diffraction (XRD). Identification and quantification of radioactive parents and daughters released from the NPs in vitro were investigated using gamma-ray spectroscopy. Results XRD and TEM analysis revealed that the NPs crystallized in the rhabdophane phase with mean diameters of 3.4 and 6.3 nm for core and core + 2 shells, respectively. The core LaPO4 NPs retained up to 88% of223 Ra over 35 days. However, in the core + 2 shells NPs, the retention of223 Ra and its daughter,211 Pb, was improved to > 99.9% over 27 days. Additionally, the retention of225 Ra/225 Ac parents was > 99.98% and ~ 80% for the221 Fr and213 Bi daughters over 35 days for the core + 2 shells NPs. Conclusions The in vitro retention of both parents and daughters results suggests that LaPO4 NPs are potentially effective carriers of radium isotopes.
ISSN:0969-8051
1872-9614
DOI:10.1016/j.nucmedbio.2015.03.007