Reversible Electroporation–Mediated Liposomal Doxorubicin Delivery to Tumors Can Be Monitored With (89)Zr-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 ((89)Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered (89)Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of (89)Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of (89)Zr-NRep in tumors. (89)Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated (89)Zr-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 (89)Zr-NRep.