title: PET neuroimaging studies of [(18)F]CABS13 in a double transgenic mouse model of Alzheimer's disease and nonhuman primates.
abstract: Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([(18)F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the "metal hypothesis of Alzheimer's disease". Herein, a practical radiosynthesis of [(18)F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [(18)F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [(18)F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 min. Temporal PET neuroimaging studies were carried out in female transgenic B6C3-Tg(APPswe,PSEN 1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7, and 10 months of age. [(18)F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal nonhuman primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable (18)F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway.
authors.affiliation: ‡Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
authors.affiliation: ‡Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Holland
authors.affiliation: ‡Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
authors.forename: Nickeisha A
authors.initials: NA
authors.lastname: Stephenson
authors.forename: Alina
authors.initials: A
authors.lastname: Kassenbrock
authors.affiliation: ‡Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Rotstein
authors.forename: Cory P
authors.initials: CP
authors.lastname: Daignault
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lewis
authors.affiliation: ‡Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.|§Advion, Inc., Ithaca, New York 14850, United States.
authors.forename: Lee
authors.initials: L
authors.lastname: Collier
authors.affiliation: ‡Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.|∥Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, United States.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: ‡Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D064847:Multimodal Imaging; D048530:Papio anubis; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000235:genetics; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D005462:Fluorine Radioisotopes; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011804:Quinolines; D019275:Radiopharmaceuticals
keywords: APP/PS1; [18F]CABS13; metal hypothesis of Alzheimer’s disease; nonhuman primates; rodents; transgenic mice