title: Gallium-68 Complexes Conjugated to Pittsburgh Compound B: Radiolabeling and Biological Evaluation.
abstract: The aim of this work is to develop an efficient and fully automated radiosynthesis of three derivatives of the Pittsburgh compound B labeled with gallium-68 for the detection of amyloid plaques.
  
  
  
  The radiolabeling of the precursors and purification of the radiolabeled agents by high pressure liquid chromatography has been studied prior to their in vitro and in vivo evaluations.
  
  
  
  The complete process led, in 50 min, to pure Ga-68 products in a 12-38 % yield and with appreciable specific radioactivity (SRA, 85-168 GBq/μmol) which enabled us to demonstrate a considerable in vivo stability of the products. Unfortunately, this result was associated with a poor blood-brain barrier (BBB) permeability and a limited uptake of our compounds by amyloid deposits was observed by in vitro autoradiography.
  
  
  
  Although we have not yet identified a compound able to significantly mark cerebral amyloidosis, this present investigation will likely contribute to the development of more successful Ga-68 radiotracers.
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France. cressier@cyceron.fr.|CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France. cressier@cyceron.fr.|Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France. cressier@cyceron.fr.
authors.forename: Damien
authors.initials: D
authors.lastname: Cressier
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France.|CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.|Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Dhilly
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France.|CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.|Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.
authors.forename: Thang T
authors.initials: TT
authors.lastname: Cao Pham
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France.|CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.|Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fillesoye
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France.|CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.|Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gourand
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France.|CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.|Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.
authors.forename: Auriane
authors.initials: A
authors.lastname: Maïza
authors.affiliation: Centre de Biophysique Moléculaire UPR 4301, CNRS, Université d'Orléans, 45071, Orléans, France.|Department of Life Sciences and Coimbra Chemistry Center, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: André F
authors.initials: AF
authors.lastname: Martins
authors.affiliation: Centre de Biophysique Moléculaire UPR 4301, CNRS, Université d'Orléans, 45071, Orléans, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Morfin
authors.affiliation: Department of Life Sciences and Coimbra Chemistry Center, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
authors.affiliation: Centre de Biophysique Moléculaire UPR 4301, CNRS, Université d'Orléans, 45071, Orléans, France.
authors.forename: Éva
authors.initials: É
authors.lastname: Tóth
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France.|CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.|Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France.
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles
keywords: Alzheimer’s disease; Automated radiosynthesis; Autoradiography; Cerebral amyloidopathies; Gallium-68; PET; PIB; Radiometabolism