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Title: LnPO 4 Nanoparticles Doped with Ac-225 and Sequestered Daughters for Targeted Alpha Therapy

For targeted alpha therapy (TAT) with 225Ac, daughter radioisotopes from the parent emissions should be controlled. We report on a second-generation layered nanoparticle (NP) with improved daughter retention that can mediate TAT of lung tumor colonies. NPs of La3+, Gd3+, and 225Ac3+ ions were coated with additional layers of GdPO4 and then coated with gold via citrate reduction of NaAuCl4. MAb 201b, targeting thrombomodulin in lung endothelium, was added to a polyethylene glycol (dPEG)-COOH linker. Furthermore, we quantified the NPs:mAb ratio by labeling the mAb with 125I. NPs showed 30% injected dose/organ antibody-mediated uptake in the lung, which increased to 47% in mice pretreated with clodronate liposomes to reduce phagocytosis. Retention of daughter 213Bi in lung tissue was more than 70% at one hour and about 90% at 24 hours postinjection. Treatment of mice with lung-targeted 225Ac NP reduced EMT-6 lung colonies relative to cold antibody competition for targeting or phosphate-buffered saline injected controls. Finally, we show that LnPO4 NPs represent a viable solution to deliver the 225Ac as an in vivo α generator. The NPs successfully retain a large percentage of the daughter products without compromising the tumoricidal properties of the α-radiation.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [4]
  1. Univ. of Missouri, Columbia, MO (United States). Dept. of Chemistry and Univ. of Missouri Research Reactor; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Nuclear Safety and Isotopes Technology Division
  2. Univ. of Missouri, Columbia, MO (United States). Dept. of Chemistry and Univ. of Missouri Research Reactor
  3. Univ. of Missouri, Columbia, MO (United States). Dept. of Pathology; Univ. of Missouri, Columbia, MO (United States). Dept. of Electrical and Computer Engineering
  4. Univ. of Tennessee, Knoxville, TN (United States). Graduate School of Medicine
  5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Nuclear Safety and Isotopes Technology Division
Publication Date:
OSTI Identifier:
1122677
DOE Contract Number:
AC05-00OR22725
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cancer Biotherapy & Radiopharmaceuticals; Journal Volume: 29; Journal Issue: 1
Publisher:
Mary Ann Liebert, Inc.
Research Org:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS)
Sponsoring Org:
USDOE Office of Nuclear Energy (NE)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE