title: Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for (223)Ra and (225)Ra for targeted alpha therapy.
abstract: BACKGROUND
  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, (225)Ra, and (225)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 either (223)Ra or(225)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 either (223)Ra or (225)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 6.3nm for core and core+2 shells, respectively. The core LaPO4 NPs retained up to 88% of (223)Ra over 35days. However, in the core+2 shells NPs, the retention of (223)Ra and its daughter, (211)Pb, was improved to >99.9% over 27days. Additionally, the retention of (225)Ra/(225)Ac parents was >99.98% and ~80% for the (221)Fr and (213)Bi 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.
authors.affiliation: Department of Mining and Nuclear Engineering, Missouri University for Science and Technology, Rolla, MO 65401; Center for Nanophase Materials Sciences and Nuclear Safety and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831.
authors.forename: J V
authors.initials: JV
authors.lastname: Rojas
authors.affiliation: Center for Nanophase Materials Sciences and Nuclear Safety and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831.
authors.forename: J D
authors.initials: JD
authors.lastname: Woodward
authors.affiliation: Center for Nanophase Materials Sciences and Nuclear Safety and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831; Provision Center for Biomedical Research, Knoxville, TN 37909.
authors.forename: N
authors.initials: N
authors.lastname: Chen
authors.affiliation: Center for Nanophase Materials Sciences and Nuclear Safety and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rondinone
authors.affiliation: Department of Mining and Nuclear Engineering, Missouri University for Science and Technology, Rolla, MO 65401.
authors.forename: C H
authors.initials: CH
authors.lastname: Castano
authors.affiliation: Center for Nanophase Materials Sciences and Nuclear Safety and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831. Electronic address: mirzadehs@ornl.gov.
authors.forename: S
authors.initials: S
authors.lastname: Mirzadeh
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D004058:Diffusion; D007811:Lanthanum / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011883:Radium / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D053769:Nanocapsules; D010710:Phosphates; D019275:Radiopharmaceuticals; D007811:Lanthanum; D011883:Radium
keywords: Actinium-225; Lanthanum phosphate; Radioactive nanoparticles; Radium-223; Radium-225; Targeted alpha therapy; Targeted radioimmunotherapy; in-vitro retention; in-vivo generators