Title

Synthesis and Characterization of Lanthanum Phosphate Nanoparticles as Carriers for ²²³Ra and ²²⁵Ra 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 as223Ra, 225Ra, and 225Ac, 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 either 223Ra or225Ra/225Ac, 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 either 223Ra or 225Ra/225Ac, 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 6.3nm for core and core + 2 shells, respectively. The core LaPO4 NPs retained up to 88% of 223Ra over 35days. However, in the core + 2 shells NPs, the retention of 223Ra and its daughter, 211Pb, was improved to > 99.9% over 27days. Additionally, the retention of 225Ra/225Ac parents was > 99.98% and ~80% for the 221Fr and 213Bi daughters over 35days 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.

Department(s)

Mining and Nuclear Engineering

Keywords and Phrases

Actinium-225; In-vitro retention; In-vivo generators; Lanthanum phosphate; Radioactive nanoparticles; Radium-223; Radium-225; Targeted alpha therapy; Targeted radioimmunotherapy

International Standard Serial Number (ISSN)

0969-8051

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2015 Elsevier Inc., All rights reserved.

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