Marie Médoc1,2,3, Martine Dhilly1,2,3, Lidia Matesic4, Jérôme Toutain2,3, Anwen M Krause-Heuer4, Jérôme Delamare1,2,3, Benjamin H Fraser4, Omar Touzani2,3, Louisa Barré1,2,3, Ivan Greguric4, Franck Sobrio5,6,7. 1. CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France. 2. CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France. 3. Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France. 4. Life Sciences Division, Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW, 2232, Australia. 5. CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France. sobrio@cyceron.fr. 6. CNRS, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France. sobrio@cyceron.fr. 7. Université de Caen Basse-Normandie, UMR 6301 ISTCT, GIP Cyceron, BP 5229, F-14074, Caen, France. sobrio@cyceron.fr.
Abstract
PURPOSE: 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. PROCEDURES: 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.
PURPOSE: The first biological evaluation of two potent fluorine-18 radiolabelled inhibitors of caspase-3/7 was achieved in a cerebral strokerat model to visualize apoptosis. PROCEDURES: 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 ratstroke 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.
Entities:
Keywords:
Apoptosis; Caspase-3 inhibitors; Cerebral stroke; Fluorine-18; In vivo evaluation; Isatins; Ischemia; PET
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