Enhanced retention of the α-particle-emitting daughters of actinium-225 by liposome carriers Journal Article
| Authors: | Sofou, S.; Kappel, B. J.; Jaggi, J. S.; McDevitt, M. R.; Scheinberg, D. A.; Sgouros, G. |
| Article Title: | Enhanced retention of the α-particle-emitting daughters of actinium-225 by liposome carriers |
| Abstract: | 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. © 2007 American Chemical Society. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; animal cell; mouse; cell line, tumor; statistical significance; drug retention; nuclear medicine; antibodies; trastuzumab; radiation dose distribution; drug conjugation; liposome; liposomes; drug carrier; internalization; lipid vesicle; phospholipid; cryoelectron microscopy; microscopy, electron, transmission; antibody labeling; alpha radiation; alpha particles; actinium; actinium 225; bismuth 213; phospholipid membrane; receptor antibody; epidermal growth factor receptor 2 antibody; microencapsulation |
| Journal Title: | Bioconjugate Chemistry |
| Volume: | 18 |
| Issue: | 6 |
| ISSN: | 1043-1802 |
| Publisher: | American Chemical Society |
| Date Published: | 2007-11-01 |
| Start Page: | 2061 |
| End Page: | 2067 |
| Language: | English |
| DOI: | 10.1021/bc070075t |
| PUBMED: | 17935286 |
| PROVIDER: | scopus |
| PMCID: | PMC2582153 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 17 November 2011" - "CODEN: BCCHE" - "Source: Scopus" |
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4Sofou -
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Jaggi -
144Mcdevitt -
499Scheinberg -
28
Kappel
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