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 ((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.
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Centro de Investigación en Red de Enfermedades Respiratorias, 28029 Madrid, Spain.|Advanced Imaging Unit, Centro Nacional de Investigaciones Cardiovasculares, CNIC, 28029 Madrid, Spain.
Carlos
C
Pérez-Medina
Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, New York 10065, USA.
Dalya
D
Abdel-Atti
Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, New York 10065, USA.
Jun
J
Tang
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Yiming
Y
Zhao
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Zahi A
ZA
Fayad
Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, New York 10065, USA.|Department of Radiology, Weill Cornell Medical College, New York, New York 10065, USA.|Molecular Pharmacology &Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Jason S
JS
Lewis
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Department of Medical Biochemistry, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
Willem J M
WJM
Mulder
Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, New York 10065, USA.|Department of Radiology, Weill Cornell Medical College, New York, New York 10065, USA.
Thomas
T
Reiner
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D016019:Survival Analysis; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014018:Tissue Distribution; D015040:Zirconium / Q000008:administration & dosage*
D000903:Antibiotics, Antineoplastic; D019275:Radiopharmaceuticals; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D015040:Zirconium