A novel liposome radiolabeling method using 99mTc-" SNS/S" complexes: In vitro and in vivo evaluation

Ande Bao, Beth Goins, Robert Klipper, George Negrete, Mathew Mahindaratne, William T. Phillips

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Liposomes are important carriers for controlled drug release, for gene or antisense therapy, and for immunization. Radiolabeled liposomes can be used to evaluate the in vivo behavior of different liposome formulations, as well as for diagnostic imaging and radionuclide therapy. A novel method for radiolabeling liposomes with 99mTc-"SNS/S" complexes is introduced. This labeling method can be applied to liposome radiolabeling with not only 99mTc but also two therapeutic radionuclides, 186Re and 188Re. Liposomes encapsulating glutathione (GSH) were studied for 99mTc labeling. N,N-bis(2-mercaptoethyl)-N′ ,N′-diethyl-ethylenediamine (BMEDA), N,N-bis(2-mercaptoethyl) -1-butylamine (BMBuA), and benzene thiol (BT) were investigated to make 99mTc-"BMEDA", 99mTc-"BMEDA + BT", 99mTc-"BMBuA", and 99mTc-"BMBuA + BT", for liposome labeling. The labeling efficiencies of 99mTc-GSH liposomes were from 36.9 to 69.2%. After incubation in serum, 99mTc-GSH liposomes labeled with 99mTc-"BMEDA" or 99mTc-"BMEDA + BT" had the best labeling stability of the formulations tested. Distribution studies after intravenous injection of 99mTc-liposomes composed of distearoyl phosphatidylcholine (DSPC) and cholesterol had a slow blood clearance and a high spleen accumulation demonstrating the in vivo labeling stability of the radiolabeled liposomes. The 99mTc-liposomes have great potential as a radiopharmaceutical system for evaluating various kinds of liposomes with different lipid composition, for evaluating in advance a subsequent radionuclide therapy using 186Re or 188Re labeled liposomes and for diagnostic imaging.

Original languageEnglish (US)
Pages (from-to)1893-1904
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume92
Issue number9
DOIs
StatePublished - Sep 1 2003

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Keywords

  • "SNS/S" complexes
  • Liposomes
  • Radiolabeling
  • Stability
  • Technetium-99m

ASJC Scopus subject areas

  • Pharmaceutical Science

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