Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 12, Issue -, Pages 3281-+Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S134379
Keywords
liposome; zirconium-89; PET; pharmacokinetics
Funding
- King's College London K.C. Wong Postdoctoral Fellowships [KCWO/413/2015]
- Rosetrees Trust PhD studentship [A1084]
- Biomedical Research Centre Award
- King's College London
- King's College Hospital NHS Foundation Trust
- Centre of Excellence in Medical Engineering - Wellcome Trust
- EPSRC [WT088641/Z/09/Z]
- UCL Comprehensive Cancer Imaging Centre - CRUK
- MRC
- DoH (England)
- Cancer Research UK [16463] Funding Source: researchfish
- Rosetrees Trust [M545] Funding Source: researchfish
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Liposomal nanoparticles are versatile drug delivery vehicles that show great promise in cancer therapy. In an effort to quantitatively measure their in vivo pharmacokinetics, we developed a highly efficient Zr-89 liposome-labeling method based on a rapid ligand exchange reaction between the membrane-permeable Zr-89(8-hydroxyquinolinate)(4) complex and the hydrophilic liposomal cavity-encapsulated deferoxamine (DFO). This novel Zr-89-labeling strategy allowed us to prepare radiolabeled forms of a folic acid (FA)-decorated active targeting Zr-89-FA-DFO-liposome, a thermosensitive Zr-89-DFO-liposome, and a renal avid Zr-89-PEGDFO- liposome at room temperature with near-quantitative isolated radiochemical yields of 98%+/- 1% (n=6), 98%+/- 2% (n=5), and 97%+/- 1% (n=3), respectively. These Zr-89- labeled liposomal nanoparticles showed remarkable stability in phosphate-buffered saline and serum at 37 degrees C without leakage of radioactivity for 48 h. The uptake of Zr-89-FA-DFO-liposome by the folate receptor-overexpressing KB cells was almost 15-fold higher than the Zr-89-DFO-liposome in vitro. Positron emission tomography imaging and ex vivo biodistribution studies enabled us to observe the heterogeneous distribution of the Zr-89-FA-DFO-liposome and Zr-89-DFO-liposome in the KB tumor xenografts, the extensive kidney accumulation of the Zr-89-FA-DFO-liposome and Zr-89-PEG-DFO-liposome, and the different metabolic fate of the free and liposome-encapsulated Zr-89- DFO. It also unveiled the poor resistance of all three liposomes against endothelial uptake resulting in their catabolism and high uptake of free Zr-89 in the skeleton. Thus, this technically simple Zr-89-labeling method would find widespread use to guide the development and clinical applications of novel liposomal nanomedicines.
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