Journal
ACS NANO
Volume 10, Issue 11, Pages 10294-10307Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.6b05935
Keywords
nanomedicine; PET imaging tumor; metastasis; drug delivery; liposomes
Categories
Funding
- King's College London
- UCL Comprehensive Cancer Imaging Centre - CRUK
- EPSRC
- MRC
- DoH (England)
- Centre of Excellence in Medical Engineering - Wellcome Trust
- EPSRC [WT 088641/Z/09/Z]
- Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's & St Thomas' NHS Foundation Trust
- MRC [MC_PC_14105] Funding Source: UKRI
- Cancer Research UK [16463, 21153] Funding Source: researchfish
- Medical Research Council [MC_PC_14105] Funding Source: researchfish
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The clinical value of current and future nano medicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as liposomal drugs with PET radionuclides will have a wide impact in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling method that exploits the metal-chelating properties of certain drugs (e.g., bisphosphonates such as alendronate and anthracyclines such as doxorubicin) and widely used ionophores to achieve excellent radiolabeling yields, purities, and stabilities with Zr-89, Mn-52, and Cu-64, and without the requirement of modification of the nanomedicine components. In a model of metastatic breast cancer, we demonstrate that this technique allows quantification of the biodistribution of a radiolabeled stealth liposomal nanomedicine containing alendronate that shows high uptake in primary tumors and metastatic organs. The versatility, efficiency, simplicity, and GMP compatibility of this method may enable submicrodosing imaging studies of liposomal nanomedicines containing chelating drugs in humans and may have clinical impact by facilitating the introduction of image-guided therapeutic strategies in current and future nanomedicine clinical studies.
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