LnPO4 nanoparticles doped with Ac-225 and sequestered daughters for targeted alpha therapy

Mark F. McLaughlin, David Robertson, Paul H. Pevsner, Jonathan Wall, Saed Mirzadeh, Stephen Kennel

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

For targeted alpha therapy (TAT) with 225Ac, daughter radioisotopes from the parent emissions should be controlled. Here, we report on a second-generation layered nanoparticle (NP) with improved daughter retention that can mediate TAT of lung tumor colonies. NPs of La3+, Gd 3+, 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. The NPs:mAb ratio was quantified 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. We conclude 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.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalCancer Biotherapy and Radiopharmaceuticals
Volume29
Issue number1
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

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Nanoparticles
Lung
Therapeutics
Clodronic Acid
Thrombomodulin
Antibodies
Phagocytosis
Liposomes
Citric Acid
Radioisotopes
Gold
Endothelium
Phosphates
Ions
Radiation
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

LnPO4 nanoparticles doped with Ac-225 and sequestered daughters for targeted alpha therapy. / McLaughlin, Mark F.; Robertson, David; Pevsner, Paul H.; Wall, Jonathan; Mirzadeh, Saed; Kennel, Stephen.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 29, No. 1, 01.02.2014, p. 34-41.

Research output: Contribution to journalArticle

McLaughlin, Mark F. ; Robertson, David ; Pevsner, Paul H. ; Wall, Jonathan ; Mirzadeh, Saed ; Kennel, Stephen. / LnPO4 nanoparticles doped with Ac-225 and sequestered daughters for targeted alpha therapy. In: Cancer Biotherapy and Radiopharmaceuticals. 2014 ; Vol. 29, No. 1. pp. 34-41.
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