title: In Vivo Evaluation of Radiofluorinated Caspase-3/7 Inhibitors as Radiotracers for Apoptosis Imaging and Comparison with [18F]ML-10 in a Stroke Model in the Rat.
abstract: OBJECTIVE
  The first biological evaluation of two potent fluorine-18 radiolabelled inhibitors of caspase-3/7 was achieved in a cerebral stroke rat model to visualize apoptosis.
  
  
  METHODS
  In vivo characteristics of isatins [(18)F]-2 and [(18)F]-3 were studied and compared by μPET to previously described 1-[4-(2-[(18)F]fluoroethyl)benzyl]-5-(2-methoxymethylpyrrolidin-1-ylsulfonyl)isatin ([(18)F]-1) and to 2-(5-[(18)F]fluoropentyl)-2-methyl-malonic acid ([(18)F]ML-10) used as a reference radiotracer in a rat stroke model.
  
  
  RESULTS
  [(18)F]-2 and [(18)F]-3 were radiolabelled with high radiochemical purity and high specific radioactivity. Radioactivity uptakes in ischemic and contralateral brain regions were weak for the three radiolabelled isatins and lower for [(18)F]ML-10. In μPET, time activity curves showed significant uptake differences between both regions of interest for [(18)F]-1 after 45 min. No differences were observed for [(18)F]ML-10.
  
  
  CONCLUSIONS
  Radiolabelled isatins are more promising radiotracers to image apoptosis than [(18)F]ML-10 in this stroke animal model without craniectomy. In particular, [(18)F]-1 presented significant uptake in apoptotic area 45 min after administration.
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Médoc
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Dhilly
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW, 2232, Australia.
authors.forename: Lidia
authors.initials: L
authors.lastname: Matesic
authors.affiliation: CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW, 2232, Australia.
authors.forename: Anwen M
authors.initials: AM
authors.lastname: Krause-Heuer
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delamare
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW, 2232, Australia.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Fraser
authors.affiliation: CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Touzani
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France.|Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France.
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW, 2232, Australia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France. sobrio@cyceron.fr.|CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France. sobrio@cyceron.fr.|Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France. sobrio@cyceron.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Sobrio
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D007510:Isatin / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008764:Methylmalonic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D057054:Molecular Imaging / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000000981:diagnostic imaging* / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: C532430:5-fluoropentyl-2-methylmalonic acid; D061945:Caspase Inhibitors; D019275:Radiopharmaceuticals; D007510:Isatin; D008764:Methylmalonic Acid; D053148:Caspase 3; D053179:Caspase 7
keywords: Apoptosis; Caspase-3 inhibitors; Cerebral stroke; Fluorine-18; In vivo evaluation; Isatins; Ischemia; PET