Nanoreporter PET predicts the efficacy of anti-cancer nanotherapy

The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co-injecting Doxil and a Zirconium-89 nanoreporter (Zr-89-NRep) allows precise doxorubicin (DOX) quantification. Importantly, Zr-89-NRep uptake also correlates with other types of nanoparticles' tumour accumulation. Zr-89-NRep PET imaging reveals remarkable accumulation heterogeneity independent of tumour size. We subsequently demonstrate that mice with 425 mg kg(-1) DOX accumulation in tumours had significantly better growth inhibition and enhanced survival. This non-invasive imaging tool may be developed into a robust inclusion criterion for patients amenable to nanotherapy.We thank the Small Animal Imaging Core, the Radiochemistry and Molecular Imaging Probes Core and the Molecular Cytology Core at Memorial Sloan Kettering Cancer Center for support. This work was supported by National Institutes of Health grants NIH 1 R01 HL125703 (W.J.M.M.), R01CA155432 (W.J.M.M.), R01 HL118440 (W.J.M.M.) and NWO Vidi (W.J.M.M.), K25 EB016673 (T.R.) and P30 CA008748, and the CNIC CardioImage program (C.P.M). The authors also thank the Center for Molecular Imaging and Nanotechnology (CMINT) for financial support (T.R.), and K. Joyes for editing the manuscript.S