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 as(223)Ra, Ra-225, and Ac-225, are of special interest for radiotherapeutic applications as they emit multiple alpha-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 nanopartides (NPs) (NPs with 2 layers of cold LaPO4 deposited on the core surfaces) were synthesized containing either Ra-223 or Ra-225/Ac-225, 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 Ra-223 or Ra-225/Ac-225, with 1 equivalent of sodium tripolyphosphate (TPP) under moderate heating and purified by membrane dialysis. Core-shell NPs were also synthesized with one (core + I 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 63 nm for core and core + 2 shells, respectively. The core LaPO4 NPs retained up to 88% of Ra-223 over 35 days. However, in the core + 2 shells NPs, the retention of Ra-223 and its daughter, Pb-211, was improved to >99.9% over 27 days. Additionally, the retention of Ra-225/Ac-225 parents was >99.98% and -80% for the Fr-221 and Bi-213 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. (C) 2015 Elsevier Inc. All rights reserved.