title: A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting.
abstract: Advances in preclinical molecular imaging have generated new opportunities to noninvasively visualize the biodistribution and tumor targeting of nanoparticle therapeutics. Capitalizing on recent achievements in this area, we sought to develop an (89)Zr-based labeling strategy for liposomal nanoparticles that accumulate in tumors via passive targeting mechanisms.
  
  
  METHODS
  (89)Zr-labeled liposomes were prepared using 2 different approaches: click labeling and surface chelation. Pharmacokinetic and biodistribution studies, as well as PET/CT imaging of the radiolabeled nanoparticles, were performed on a mouse model of breast cancer. In addition, a dual PET/optical probe was prepared by incorporation of a near-infrared fluorophore and tested in vivo by PET and near-infrared fluorescence imaging.
  
  
  RESULTS
  The surface chelation approach proved to be superior in terms of radiochemical yield and stability, as well as in vivo performance. Accumulation of these liposomes in tumor peaked at 24 h after injection and was measured to be 13.7 ± 1.8 percentage injected dose per gram. The in vivo performance of this probe was not essentially perturbed by the incorporation of a near-infrared fluorophore.
  
  
  CONCLUSIONS
  We have developed a highly modular and efficient strategy for the labeling of liposomal nanoparticles with (89)Zr. In xenograft and orthotopic mouse models of breast cancer, we demonstrated that the biodistribution of these nanoparticles can be visualized by PET imaging. In combination with a near-infrared dye, these liposomal nanoparticles can serve as bimodal PET/optical imaging agents. The liposomes target malignant growth, and their bimodal features may be useful for simultaneous PET and intraoperative imaging.
authors: Centro de Investigación en Red de Enfermedades Respiratorias, Madrid, Spain Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Carlos
authors: C
authors: Pérez-Medina
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Dalya
authors: D
authors: Abdel-Atti
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Yachao
authors: Y
authors: Zhang
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Valerie A
authors: VA
authors: Longo
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Chrisopher P
authors: CP
authors: Irwin
authors: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York Cluster for Molecular Imaging, Faculty of Health Sciences and Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen, Denmark.
authors: Tina
authors: T
authors: Binderup
authors: Centro de Investigación en Red de Enfermedades Respiratorias, Madrid, Spain Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain.
authors: Jesús
authors: J
authors: Ruiz-Cabello
authors: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Zahi A
authors: ZA
authors: Fayad
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York; and Center for Molecular Imaging and Nanotechnology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Jason S
authors: JS
authors: Lewis
authors: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Willem J M
authors: WJ
authors: Mulder
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York Center for Molecular Imaging and Nanotechnology, Memorial Sloan-Kettering Cancer Center, New York, New York reinert@mskcc.org.
authors: Thomas
authors: T
authors: Reiner
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry; D014057:Tomography, X-Ray Computed / Q000379:methods; D015040:Zirconium / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D019275:Radiopharmaceuticals; D015040:Zirconium
keywords: 89Zr; PET; breast cancer; liposomes; near-infrared imaging