Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 11, Issue 1, Pages 155-165Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2014.08.011
Keywords
Liposome; Cu-64; PET imaging; Tumor deposition; Drug delivery
Funding
- Merrimack Pharmaceuticals
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Effective drug delivery to tumors is a barrier to treatment with nanomedicines. Non-invasively tracking liposome biodistribution and tumor deposition in patients may provide insight into identifying patients that are well-suited for liposomal therapies. We describe a novel gradient-loadable chelator, 4-DEAP-ATSC, for incorporating Cu-64 into liposomal therapeutics for positron emission tomographic (PET). Cu-64 chelated to 4-DEAP-ATSC (>94%) was loaded into PEGylated liposomal doxorubicin (PLD) and HER2-targeted PLD (MM-302) with efficiencies >90%. Cu-64-MM-302 was stable in human plasma for at least 48 h. PET/CT imaging of xenografts injected with Cu-64-MM-302 revealed biodistribution profiles that were quantitatively consistent with tissue-based analysis, and tumor Cu-64 positively correlated with liposomal drug deposition. This loading technique transforms liposomal therapeutics into theranostics and is currently being applied in a clinical trial (NCT01304797) to non-invasively quantify MM-302 tumor deposition, and evaluate its potential as a prognostic tool for predicting treatment outcome of nanomedicines. From the Clinical Editor: This study describes a PET-based detection method utilizing in vivo localization of Cu-64-labeled liposomes. In addition to the presented rodent model, a clinical trial is already underway to investigate the clinical utility of this technique. (C) 2015 Elsevier Inc. All rights reserved.
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