18F-labeled-bioorthogonal liposomes for in vivo targeting Journal Article


Authors: Emmetiere, F.; Irwin, C.; Viola-Villegas, N. T.; Longo, V.; Cheal, S. M.; Zanzonico, P.; Pillarsetty, N.; Weber, W. A.; Lewis, J. S.; Reiner, T.
Article Title: 18F-labeled-bioorthogonal liposomes for in vivo targeting
Abstract: Liposomes are attractive vehicles for the controlled release of drugs and cytotoxins and have a long-standing history in medical research and clinical practice. In addition to established therapeutic indications, liposomes have several favorable properties for molecular imaging, including high stability and the ability to be labeled with radioisotopes, as well as paramagnetic and fluorescent contrast agents. However, long circulation times and difficulties in creating targeted liposomes have proven challenges for imaging. In this study, we have addressed these limitations using a recently developed strategy for bioorthogonal conjugation, the reaction between tetrazines and trans-cyclooctenes. By coating radiolabeled liposomes with trans-cyclooctene and pretargeting with a tetrazine coupled to a targeted peptide, we were able to selectively enhance the retention of liposomes and bind them to tumor tissue in live animals. The rapid reaction between tetrazines and trans-cyclooctenes allowed imaging to be performed with the short-lived PET tracer 18F, yielding signal-to-background activity ratios of 7:1. The covalent, bioorthogonally driven tumor-targeting of liposomes by in vivo click chemistry is promising and should be explored for more selective and rapid delivery of radiodiagnostics and radiotherapeutics, two classes of drugs which particularly benefit from fast clearance, low nonspecific binding, and the associated reduced toxicity to kidneys and bone marrow. © 2013 American Chemical Society.
Keywords: controlled study; unclassified drug; nonhuman; drug targeting; positron emission tomography; mass spectrometry; animal cell; mouse; ovary cancer; animal experiment; animal model; in vivo study; drug distribution; cancer cell; high performance liquid chromatography; drug half life; fluorine 18; liquid chromatography; drug conjugation; liposome; drug degradation; drug conformation; light scattering; electron spin resonance; tetrazine derivative; female; article; alicyclic hydrocarbon; trans cyclooctenes; drug decomposition; gel permeation chromatography
Journal Title: Bioconjugate Chemistry
Volume: 24
Issue: 11
ISSN: 1043-1802
Publisher: American Chemical Society  
Date Published: 2013-11-20
Start Page: 1784
End Page: 1789
Language: English
DOI: 10.1021/bc400322h
PROVIDER: scopus
PMCID: PMC3903177
PUBMED: 24180480
DOI/URL:
Notes: Export Date: 2 January 2014 -- CODEN: BCCHE -- Source: Scopus
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MSK Authors
  1. Pat B Zanzonico
    355 Zanzonico
  2. Jason S Lewis
    456 Lewis
  3. Sarah Marie Cheal
    48 Cheal
  4. Valerie Ann Longo
    37 Longo
  5. Thomas Reiner
    136 Reiner
  6. Christopher P. Irwin
    10 Irwin
  7. Wolfgang Andreas Weber
    173 Weber