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 efficient89Zr liposome-labeling method based on a rapid ligand exchange reaction between the membrane-permeable89Zr(8-hydroxyquinolinate)4 complex and the hydrophilic liposomal cavity-encapsulated deferoxamine (DFO). This novel89Zr-labeling strategy allowed us to prepare radiolabeled forms of a folic acid (FA)-decorated active targeting89Zr-FA-DFO-liposome, a thermosensitive89Zr-DFO-liposome, and a renal avid89Zr-PEG-DFO-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. These89Zr-labeled liposomal nanoparticles showed remarkable stability in phosphate-buffered saline and serum at 37°C without leakage of radioactivity for 48 h. The uptake of89Zr-FA-DFO-liposome by the folate receptor-overexpressing KB cells was almost 15-fold higher than the89Zr-DFO-liposome in vitro. Positron emission tomography imaging and ex vivo biodistribution studies enabled us to observe the heterogeneous distribution of the89Zr-FA-DFO-liposome and89Zr-DFO-liposome in the KB tumor xenografts, the extensive kidney accumulation of the89Zr-FA-DFO-liposome and89Zr-PEG-DFO-liposome, and the different metabolic fate of the free and liposome-encapsulated89Zr-DFO. It also unveiled the poor resistance of all three liposomes against endothelial uptake resulting in their catabolism and high uptake of free89Zr in the skeleton. Thus, this technically simple89Zr-labeling method would find widespread use to guide the development and clinical applications of novel liposomal nanomedicines.
CITATION STYLE
Li, N., Yu, Z., Pham, T. T., Blower, P. J., & Yan, R. (2017). A generic89zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography. International Journal of Nanomedicine, 12, 3281–3294. https://doi.org/10.2147/IJN.S134379
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