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Nanomedicine. 2015 Jan;11(1):155-65. doi: 10.1016/j.nano.2014.08.011. Epub 2014 Sep 6.

A gradient-loadable (64)Cu-chelator for quantifying tumor deposition kinetics of nanoliposomal therapeutics by positron emission tomography.

Author information

1
Merrimack Pharmaceuticals, Cambridge, MA, USA. Electronic address: hlee@merrimackpharma.com.
2
STTARR Innovation Centre, Radiation Medicine Program, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.
3
Merrimack Pharmaceuticals, Cambridge, MA, USA.
4
inviCRO, LLC, Boston, MA, USA.

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 incorporating (64)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 48h. PET/CT imaging of xenografts injected with (64)Cu-MM-302 revealed biodistribution profiles that were quantitatively consistent with tissue-based analysis, and tumor (64)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.

KEYWORDS:

(64)Cu; Drug delivery; Liposome; PET imaging; Tumor deposition

PMID:
25200610
DOI:
10.1016/j.nano.2014.08.011
[Indexed for MEDLINE]

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