Abstract: 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 ef cient 89Zr liposome-labeling method based on a rapid ligand exchange reaction between the membrane-permeable 89Zr(8-hydroxyquinolinate)4 complex and the hydrophilic liposomal cavity-encapsulated deferoxamine (DFO). This novel 89Zr-labeling strategy allowed us to prepare radiolabeled forms of a folic acid (FA)-decorated active targeting 89Zr-FA-DFO-liposome, a thermosensitive 89Zr-DFO-liposome, and a renal avid 89Zr-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. These 89Zr-labeled lipo- somal nanoparticles showed remarkable stability in phosphate-buffered saline and serum at 37°C without leakage of radioactivity for 48 h. The uptake of 89Zr-FA-DFO-liposome by the folate receptor-overexpressing KB cells was almost 15-fold higher than the 89Zr-DFO-liposome in vitro. Positron emission tomography imaging and ex vivo biodistribution studies enabled us to observe the heterogeneous distribution of the 89Zr-FA-DFO-liposome and 89Zr-DFO-liposome in the KB tumor xenografts, the extensive kidney accumulation of the 89Zr-FA-DFO-liposome and 89Zr-PEG-DFO-liposome, and the different metabolic fate of the free and liposome-encapsulated 89Zr-DFO. It also unveiled the poor resistance of all three liposomes against endothelial uptake resulting in their catabolism and high uptake of free 89Zr in the skeleton. Thus, this technically simple 89Zr-labeling method would nd widespread use to guide the development and clinical applications of novel liposomal nanomedicines.
- liposome, zirconium-89, PET, pharmacokinetics