Enhanced retention of the α-particle-emitting daughters of actinium-225 by liposome carriers

Stavroula Sofou, Barry J. Kappel, Jaspreet S. Jaggi, Michael R. McDevitt, David A. Scheinberg, George Sgouros

Research output: Contribution to journalArticlepeer-review


Targeted α-particle emitters hold great promise as therapeutics for micrometastatic disease. Because of their high energy deposition and short range, tumor targeted α-particles can result in high cancer-cell killing with minimal normal-tissue irradiation. Actinium-225 is a potential generator for α-particle therapy: it decays with a 10-day half-life and generates three α-particle-emitting daughters. Retention of 225Ac daughters at the target increases efficacy; escape and distribution throughout the body increases toxicity. During circulation, molecular carriers conjugated to 225Ac cannot retain any of the daughters. We previously proposed liposomal encapsulation of 225Ac to retain the daughters, whose retention was shown to be liposome-size dependent. However, daughter retention was lower than expected: 22% of theoretical maximum decreasing to 14%, partially due to the binding of 225Ac to the phospholipid membrane. In this study, Multivesicular liposomes (MUVELs) composed of different phospholipids were developed to increase daughter retention. MUVELs are large liposomes with entrapped smaller lipid-vesicles containing 225Ac. PEGylated MUVELs stably retained overtime 98% of encapsulated 225Ac. Retention of 213Bi, the last daughter, was 31% of the theoretical maximum retention of 213Bi for the liposome sizes studied. MUVELs were conjugated to an anti-HER2/neu antibody (immunolabeled MUVELs) and were evaluated in vitro with SKOV3-NMP2 ovarian cancer cells, exhibiting significant cellular internalization (83%). This work demonstrates that immunolabeled MUVELs might be able to deliver higher fractions of generated α-particles per targeted 225Ac compared to the relative fractions of α-particles delivered by 225Ac-labeled molecular carriers.

Original languageEnglish (US)
Pages (from-to)2061-2067
Number of pages7
JournalBioconjugate Chemistry
Issue number6
StatePublished - 2007

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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