title: Fluorine-18 labeling of three novel D-peptides by conjugation with N-succinimidyl-4-[18F]fluorobenzoate and preliminary examination by postmortem whole-hemisphere human brain autoradiography.
abstract: BACKGROUND
  β-Amyloid (Aβ) plaques and neurofibrillary tangles are the main characteristics of Alzheimer's disease (AD). Positron emission tomography (PET), a high-resolution, sensitive, and noninvasive imaging technique, has been widely utilized in visualizing the localization of plaques and tangles and thereby distinguishing between AD and healthy controls. A small 12-mer D-enantiomeric peptide (amino acid sequence=QSHYRHISPAQV), denoted as D1, has high binding affinity to Aβ in vitro in the sub-micromolar range, and consequently, its radiolabeled analogues have a potential as radioligands for visualizing amyloid plaques in vivo by PET.
  
  
  OBJECTIVE
  The aims of the present work were to develop three different potent D1 derivative peptides labeled with fluorine-18 and to examine them in the AD and control postmortem human brain by autoradiography (ARG).
  
  
  METHODS
  Three different D1 derivative peptides were radiolabeled with fluorine-18 ([(18)F]ACI-87, [(18)F]ACI-88, [(18)F]ACI-89) using the prosthetic group N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB) and purified by high performance liquid chromatography (HPLC). Preliminary ARG measurements were performed in AD and control brains.
  
  
  RESULTS
  The three fluorine-18-labeled d-peptides were obtained in a total synthesis time of 140 min with radiochemical purity higher than 98%. The specific radioactivities of the three different D1 derivative peptides were between 9 and 113 GBq/μmol. ARG demonstrated a higher radioligand uptake in the cortical gray matter and the hippocampus in the AD brain as compared to age-matched control brain.
  
  
  CONCLUSIONS
  Fluorine-18 labeling of the three novel D1 derivative peptides using [(18)F]SFB was successfully accomplished. Higher contrast between AD and control brain slices demonstrates their potential applicability for further use in vivo by PET.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska University Hospital, S-17176 Stockholm, Sweden. mahabuba.jahan@ki.se
authors.forename: Mahabuba
authors.initials: M
authors.lastname: Jahan
authors.forename: Sangram
authors.initials: S
authors.lastname: Nag
authors.forename: Raisa
authors.initials: R
authors.lastname: Krasikova
authors.forename: Urs
authors.initials: U
authors.lastname: Weber
authors.forename: Andreas
authors.initials: A
authors.lastname: Muhs
authors.forename: Andrea
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Christian
authors.initials: C
authors.lastname: Spenger
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging; D001345:Autoradiography / Q000379:methods*; D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry*; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011856:Radiographic Image Enhancement; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001565:Benzoates; C551352:D1 peptide; D005462:Fluorine Radioisotopes; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D013388:Succinimides; C075713:N-succinimidyl-4-fluorobenzoate