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

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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.


In vivo characteristics of isatins [18F]-2 and [18F]-3 were studied and compared by μPET to previously described 1-[4-(2-[18F]fluoroethyl)benzyl]-5-(2-methoxymethylpyrrolidin-1-ylsulfonyl)isatin ([18F]-1) and to 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid ([18F]ML-10) used as a reference radiotracer in a rat stroke model.


[18F]-2 and [18F]-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 [18F]ML-10. In μPET, time activity curves showed significant uptake differences between both regions of interest for [18F]-1 after 45 min. No differences were observed for [18F]ML-10.


Radiolabelled isatins are more promising radiotracers to image apoptosis than [18F]ML-10 in this stroke animal model without craniectomy. In particular, [18F]-1 presented significant uptake in apoptotic area 45 min after administration

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Marie Médoc and the project were financed by the Conseil Régional de Basse-Normandie (Lower Normandy Council). The authors thank Olivier Tirel for performing the cyclotron production. The technical assistance of Fabien Fillesoye was greatly appreciated. Lidia Matesic gratefully acknowledges the Australian Academy of Science for a France-Australia Science Innovation Collaboration Early Career Fellowship.

Conflict of Interest

The authors declare that they have no conflict of interests.

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Correspondence to Franck Sobrio.

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Médoc, M., Dhilly, M., Matesic, L. et al. 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. Mol Imaging Biol 18, 117–126 (2016).

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Key words

  • Fluorine-18
  • PET
  • Apoptosis
  • Cerebral stroke
  • Ischemia
  • Caspase-3 inhibitors
  • In vivo evaluation
  • Isatins