Reversible Electroporation–Mediated Liposomal Doxorubicin Delivery to Tumors Can Be Monitored With 89Zr-Labeled Reporter Nanoparticles

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation-related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep.