Journal of Nanomedicine & Nanotechnology

A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles and personalize their dose titration with PET

13^th International Conference and Exhibition on Nanomedicine and Pharmaceutical Nanotechnology

July 24-25, 2017 | Rome, Italy

Ran Yan

Kingâ??s College London, UK

Posters & Accepted Abstracts: J Nanomed Nanotechnol

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 and personalize dose titration, we have developed a highly efficient 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 liposomal nanoparticles showed remarkable stability in PBS 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 (PET) 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. Thus, this technically simple 89Zr labeling method would find widespread use to guide the development and clinical applications of novel liposomal nanomedicines.

Biography :

Email: ran.yan@kcl.ac.uk