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

Journal Article · Sat Feb 01 00:00:00 EST 2014 · Cancer Biotherapy & Radiopharmaceuticals

DOI:https://doi.org/10.1089/cbr.2013.1546· OSTI ID:1122677

McLaughlin, Mark F. ^[1]; Robertson, David ^[2]; Pevsner, Paul H. ^[3]; Wall, Jonathan S. ^[4]; Mirzadeh, Saed ^[5]; Kennel, Stephen J. ^[4]

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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

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.

• Research Organization: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS)
• Sponsoring Organization: USDOE Office of Nuclear Energy (NE)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 1122677
• Journal Information: Cancer Biotherapy & Radiopharmaceuticals, Vol. 29, Issue 1; ISSN 1084-9785
• Publisher: Mary Ann Liebert, Inc.
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE