Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy

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.  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 was investigated using gamma-ray spectroscopy.   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% of ²²³Ra over 35 days. However, in the core+2 shells NPs, the retention of ²²³Ra and its daughter, ²¹¹Pb, was improved to >99.9% over 27 days. Additionally, the retention of ²²⁵Ra/²²⁵Ac parents was >99.98% and ~80% for the ²²¹Fr and ²¹³Bi daughters over 35 days for the core+2 shells NPs.  The in vitro retention of both parents and daughters results suggest that LaPO₄ NPs are potentially effective carriers of radium isotopes.