Journal Article

Nanoreporter PET predicts the efficacy of anti-cancer nanotherapy

Fayad, Zahi A., Mulder, Willem J. M., Zhao, Yiming, Abdel-Atti, Dalya, Pérez-Medina, Carlos, Tang, Jun, Lewis, Jason S., Reiner, Thomas

2016

Overview

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 ( 89 Zr-NRep) allows precise doxorubicin (DOX) quantification. Importantly, 89 Zr-NRep uptake also correlates with other types of nanoparticles’ tumour accumulation. 89 Zr-NRep PET imaging reveals remarkable accumulation heterogeneity independent of tumour size. We subsequently demonstrate that mice with >25 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. Nanoparticle drug formulations are currently used as cancer treatment but the response in patients is highly variable. Here, the authors developed a Zirconium-89 nanoreporter able to predict using PET, therapeutic accumulation and efficacy of anti-cancer nanoparticle drug formulations when co-injected in a murine breast cancer model.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 59/78 / 631/1647/245/2092 / 631/67/1059 / 692/308 / Accumulation / Animals / Antibiotics, Antineoplastic - pharmacokinetics / Antibiotics, Antineoplastic - pharmacology / Anticancer properties / Biological Transport / Breast cancer / Cancer / Coinjection / Doxorubicin / Doxorubicin - analogs & derivatives / Doxorubicin - pharmacokinetics / Doxorubicin - pharmacology / Drug Administration Schedule / Female / Formulations / Growth inhibition / Heterogeneity / Humanities and Social Sciences / Humans / Mammary Neoplasms, Experimental - diagnostic imaging / Mammary Neoplasms, Experimental - mortality / Mammary Neoplasms, Experimental - pathology / Mammary Neoplasms, Experimental - therapy / Medical imaging / Mice / multidisciplinary / Nanoparticles / Nanoparticles - administration & dosage / Nanoparticles - chemistry / Nanotechnology / Patients / Polyethylene Glycols - pharmacokinetics / Polyethylene Glycols - pharmacology / Positron emission / Positron emission tomography / Positron-Emission Tomography - methods / Radiopharmaceuticals - administration & dosage / Science / Science (multidisciplinary) / Survival Analysis / Theranostic Nanomedicine - methods / Tissue Distribution / Tomography / Tumors / Zirconium / Zirconium - administration & dosage / Zirconium isotopes