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

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 [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.

Results

[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.

Conclusions

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