A gradient-loadable64 Cu-chelator for quantifying tumor deposition kinetics of nanoliposomal therapeutics by positron emission tomography

Abstract 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...

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Bibliographic Details
Published in:Nanomedicine 2015, Vol.11 (1), p.155-165
Main Authors: Lee, Helen, PhD, Zheng, Jinzi, PhD, Gaddy, Daniel, PhD, Orcutt, Kelly D., PhD, Leonard, Shannon, BS, Geretti, Elena, PhD, Hesterman, Jacob, PhD, Harwell, Catey, SB, Hoppin, Jack, PhD, Jaffray, David A., PhD, Wickham, Thomas, PhD, Hendriks, Bart S., PhD, Kirpotin, Dmitri, PhD
Format: Article
Language:English
Subjects:
Internal Medicine
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Summary:Abstract 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 incorporating64 Cu into liposomal therapeutics for positron emission tomographic (PET).64 Cu chelated to 4-DEAP-ATSC (> 94%) was loaded into PEGylated liposomal doxorubicin (PLD) and HER2-targeted PLD (MM-302) with efficiencies > 90%.64 Cu-MM-302 was stable in human plasma for at least 48 h. PET/CT imaging of xenografts injected with64 Cu-MM-302 revealed biodistribution profiles that were quantitatively consistent with tissue-based analysis, and tumor64 Cu 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 64Cu-labeled liposomes. In addition to the presented rodent model, a clinical trial is already underway to investigate the clinical utility of this technique.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2014.08.011