title: (18)F-labeled-bioorthogonal liposomes for in vivo targeting.
abstract: Liposomes are attractive vehicles for the controlled release of drugs and cytotoxins and have a long-standing history in medical research and clinical practice. In addition to established therapeutic indications, liposomes have several favorable properties for molecular imaging, including high stability and the ability to be labeled with radioisotopes, as well as paramagnetic and fluorescent contrast agents. However, long circulation times and difficulties in creating targeted liposomes have proven challenges for imaging. In this study, we have addressed these limitations using a recently developed strategy for bioorthogonal conjugation, the reaction between tetrazines and trans-cyclooctenes. By coating radiolabeled liposomes with trans-cyclooctene and pretargeting with a tetrazine coupled to a targeted peptide, we were able to selectively enhance the retention of liposomes and bind them to tumor tissue in live animals. The rapid reaction between tetrazines and trans-cyclooctenes allowed imaging to be performed with the short-lived PET tracer (18)F, yielding signal-to-background activity ratios of 7:1. The covalent, bioorthogonally driven tumor-targeting of liposomes by in vivo click chemistry is promising and should be explored for more selective and rapid delivery of radiodiagnostics and radiotherapeutics, two classes of drugs which particularly benefit from fast clearance, low nonspecific binding, and the associated reduced toxicity to kidneys and bone marrow.
authors.affiliation: Department of Radiology, ‡Department of Medical Physics, §Molecular Imaging and Therapy Service, Department of Radiology, and ∥Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center , New York, New York, 10065, United States.
authors.forename: Fabien
authors.initials: F
authors.lastname: Emmetiere
authors.forename: Christopher
authors.initials: C
authors.lastname: Irwin
authors.forename: Nerissa Therese
authors.initials: NT
authors.lastname: Viola-Villegas
authors.forename: Valerie
authors.initials: V
authors.lastname: Longo
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Cheal
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Nagavarakishore
authors.initials: N
authors.lastname: Pillarsetty
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057930:Click Chemistry; D034242:Cyclooctanes / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D049268:Positron-Emission Tomography; D013777:Tetrazoles / Q000737:chemistry
chemical_list: D034242:Cyclooctanes; D005462:Fluorine Radioisotopes; D008081:Liposomes; D004364:Pharmaceutical Preparations; D013777:Tetrazoles