In vivo evaluation of inflammatory bowel disease with the aid of μPET and the translocator protein 18 kDa radioligand [18F]DPA-714.

OBJECTIVE

The purpose of the study was to validate [18F]DPA-714, a translocator protein (TSPO) 18 kDa radioligand, as a probe to non-invasively quantify the inflammatory state in inflammatory bowel disease (IBD) animal models.

METHODS

Quantitative positron emission tomography (PET) imaging of intestinal inflammation was conducted with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) a glucose metabolism surrogate marker and [18F]DPA-714 a ligand of the 18 kDa TSPO, on two IBD models. The first model was induced using dextran sodium sulfate (DSS), creating global inflammation in the colon. The second model was induced by rectally administering trinitrobenzenesulfonic acid (TNBS), creating local and acute inflammation.

RESULTS

The level of inflammation was analyzed using PET imaging on days 7 and 8. The analysis obtained with [18F]DPA-714, yielded a significant difference between the DSS treated (0.50 ± 0.17%ID/cc) and non-treated rats (0.35 ± 0.15%ID/cc). [18F]FDG on the other hand did not yield a significant difference. We did observe a mean glucose consumption in the colon increase from 0.40 ± 0.11 %ID/cc to 0.54 ± 0.17 %ID/cc. In the TNBS model, the uptake level of [18 F]DPA-714 increased significantly from 0.46 ± 0.23%ID/cc for the non-treated group, to 1.30 ± 0.62%ID/cc for those treated. PET signal was correlated with increased TSPO expression at cellular level.

CONCLUSIONS

Results indicate that [18F]DPA-714 is suitable for studying inflammation in IBD models. [18F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level within this disease family.