title: (18)F-Based Pretargeted PET Imaging Based on Bioorthogonal Diels-Alder Click Chemistry.
abstract: A first-of-its-kind (18)F pretargeted PET imaging approach based on the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) is presented. As proof-of-principle, a TCO-bearing immunoconjugate of the anti-CA19.9 antibody 5B1 and an Al[(18)F]NOTA-labeled tetrazine radioligand were harnessed for the visualization of CA19.9-expressing BxPC3 pancreatic cancer xenografts. Biodistribution and (18)F-PET imaging data clearly demonstrate that this methodology effectively delineates tumor mass with activity concentrations up to 6.4 %ID/g at 4 h after injection of the radioligand.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Jan-Philip
authors.initials: JP
authors.lastname: Meyer
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Houghton
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Kozlowski
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Dalya
authors.initials: D
authors.lastname: Abdel-Atti
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Naga Vara Kishore
authors.initials: NV
authors.lastname: Pillarsetty
authors.affiliation: MabVax Therapeutics , 11588 Sorrento Valley Road Suite 20, San Diego, California 92121, United States.
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Scholz
authors.affiliation: Department of Chemistry, Hunter College of the City University of New York , 695 Park Avenue, New York, New York 10065, United States.|The Graduate Center, City University of New York , 365 Fifth Avenue, New York, New York 10016, United States.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Zeglis
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D057930:Click Chemistry / Q000379:methods; D061565:Cycloaddition Reaction / Q000379:methods; D034242:Cyclooctanes / Q000737:chemistry* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D034242:Cyclooctanes; D005462:Fluorine Radioisotopes; D018796:Immunoconjugates; D019275:Radiopharmaceuticals; C578959:carbohydrate antigen 199, human