title: (18)F-Labeled benzylideneaniline derivatives as new ligands for beta-amyloid plaque imaging in Alzheimer's disease.
abstract: BACKGROUND
  Noninvasive early detection of beta-amyloid (Abeta) plaques might be useful for the treatment of patients with Alzheimer's disease (AD). We herein describe the synthesis of (18)F-labeled benzylideneaniline derivatives using a novel labeling approach for imaging Abeta plaques in AD patients.
  
  
  METHODS
  Benzylidenaniline derivatives were synthesized by reacting fluorobenzaldehyde and corresponding aniline derivatives. Fluorobenzaldehyde was labeled with (18)F by incubating [(18)F]fluoride with N,N,N-trimethylbenzaldehyde in the presence of tetrabutylammonium bicarbonate. In vitro binding assay, stability test and biodistribution study were performed.
  
  
  RESULTS
  These compounds were stable at alkaline pH (pH >9); however, they were hydrolyzed rapidly at physiological pH (pH approximately 7.4). The K(i) values of amine-containing benzylideneaniline derivatives for Abeta(1-40) and Abeta(1-42) aggregates were 26-78 nM. These (18)F-labeled benzylideneaniline derivatives showed high brain uptake and rapid clearance after intravenous administration in normal mice (1.8-3.1%ID/g at 2 min and 0.1-1.2%ID/g at 30 min). The low level of bone activity at 30 min indicated that these (18)F-labeled benzylideneanilines are not prone to defluorination. Furthermore, the compounds have suitable lipophilicity - a property required to penetrate the blood-brain barrier.
  
  
  CONCLUSIONS
  These results showed that the instability of these compounds could cause a higher early phase/late phase ratio due to rapid clearance in the normal brain. The findings from this study suggest that these (18)F-labeled benzylideneaniline derivatives are feasible for the imaging of Abeta plaques.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine and Institute of Radiation Medicine, Jongno-gu, Seoul 110-744, South Korea. yes2hack@snu.ac.kr
authors.forename: Hak Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Ganesha
authors.initials: G
authors.lastname: Rai
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Chang
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyung Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: Jung Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001597:Benzylidene Compounds / Q000378:metabolism*; D001812:Blood-Brain Barrier; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D001597:Benzylidene Compounds; D005462:Fluorine Radioisotopes; D008024:Ligands; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)