title: (68)Ga-Bivalent Polypegylated Styrylpyridine Conjugates for Imaging Aβ Plaques in Cerebral Amyloid Angiopathy.
abstract: Aβ plaques deposited on blood vessels are associated with cerebral amyloid angiopathy (CAA). In an effort to selectively map these Aβ plaques, we are reporting a new series of (68)Ga labeled styrylpyridine derivatives with high molecular weights. In vitro binding to Aβ plaques in post-mortem Alzheimer's disease (AD) brain tissue showed that these (68)Ga labeled bivalent styrylpyridines displayed good affinities and specificity (Ki < 30 nM). In vitro autoradiography using post-mortem AD brain sections showed specific binding of these (68)Ga complexes to Aβ plaques. Biodistribution studies in normal mice showed very low initial brain uptakes (<0.3% dose/g) indicating a low blood-brain barrier (BBB) penetration. The preliminary results suggest that (68)Ga labeled bivalent styrylpyridines may be promising candidates as PET imaging radiotracers for detecting CAA.
authors.affiliation: Beijing Institute for Brain Disorders, Capital Medical University , Beijing, 100069, China.|Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Zha
authors.affiliation: Beijing Institute for Brain Disorders, Capital Medical University , Beijing, 100069, China.|Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Jin
authors.initials: J
authors.lastname: Song
authors.affiliation: Five Eleven Pharma Inc. , Philadelphia, Pennsylvania 19104, United States.|Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Seok Rye
authors.initials: SR
authors.lastname: Choi
authors.affiliation: Beijing Institute for Brain Disorders, Capital Medical University , Beijing, 100069, China.|Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Zehui
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Five Eleven Pharma Inc. , Philadelphia, Pennsylvania 19104, United States.|Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Karl
authors.initials: K
authors.lastname: Ploessl
authors.affiliation: Five Eleven Pharma Inc. , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Smith
authors.affiliation: Beijing Institute for Brain Disorders, Capital Medical University , Beijing, 100069, China.|Five Eleven Pharma Inc. , Philadelphia, Pennsylvania 19104, United States.|Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Hank
authors.initials: H
authors.lastname: Kung
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000150:complications*; D005710:Gallium Radioisotopes; D051379:Mice; D058225:Plaque, Amyloid / Q000150:complications* / Q000000981:diagnostic imaging*; D011092:Polyethylene Glycols / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D013343:Styrenes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D011725:Pyridines; D013343:Styrenes; C003347:4-stilbazole; D011092:Polyethylene Glycols