Damien Cressier1,2,3, Martine Dhilly4,5,6, Thang T Cao Pham4,5,6, Fabien Fillesoye4,5,6, Fabienne Gourand4,5,6, Auriane Maïza4,5,6, André F Martins7,8, Jean-François Morfin7, Carlos F G C Geraldes8, Éva Tóth7, Louisa Barré4,5,6. 1. CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France. cressier@cyceron.fr. 2. CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France. cressier@cyceron.fr. 3. Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France. cressier@cyceron.fr. 4. CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France. 5. CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France. 6. Université de Caen Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, 14074, Caen, France. 7. Centre de Biophysique Moléculaire UPR 4301, CNRS, Université d'Orléans, 45071, Orléans, France. 8. Department of Life Sciences and Coimbra Chemistry Center, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
Abstract
PURPOSE: 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. PROCEDURES: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. PROCEDURES: 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. RESULTS: 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. CONCLUSION: 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.
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