# In vivo Evaluation of Inflammatory Bowel Disease with the Aid of μPET and the Translocator Protein 18 kDa Radioligand [18F]DPA-714

**Authors:** Nicholas Bernards, Géraldine Pottier, Benoit Thézé, Frédéric Dollé, Raphael Boisgard

PMC · DOI: 10.1007/s11307-014-0765-9 · Molecular Imaging and Biology · 2014-07-12

## TL;DR

This study shows that [18F]DPA-714 can effectively track inflammation in animal models of inflammatory bowel disease using PET imaging.

## Contribution

The study validates [18F]DPA-714 as a novel radioligand for non-invasive quantification of intestinal inflammation in IBD models.

## Key findings

- [18F]DPA-714 showed significant differences in uptake between inflamed and non-inflamed DSS-treated rats.
- In the TNBS model, [18F]DPA-714 uptake increased significantly in treated animals compared to controls.
- PET imaging with [18F]DPA-714 correlated with increased TSPO expression at the cellular level.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Proteins:** TSPO (translocator protein)
- **Chemicals:** trinitrobenzenesulfonic acid (PubChem CID 11045), [18F]DPA-714 (PubChem CID 23582365), [18F]FDG (PubChem CID 68614)
- **Diseases:** inflammatory bowel disease (MONDO:0005265), IBD (MONDO:0005265)

## Full-text entities

- **Genes:** Aif1 (allograft inflammatory factor 1) [NCBI Gene 29427] {aka BART-1, Bart1, iba1, mrf-1}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Tspo (translocator protein) [NCBI Gene 24230] {aka Bzrp, MBR, PTBZR02, Ptbzr, RATPTBZR02}, TSPO (translocator protein) [NCBI Gene 706] {aka BPBS, BZRP, DBI, IBP, MBR, PBR}
- **Diseases:** loss of (MESH:D016388), motility (MESH:D015835), cancer (MESH:D009369), weight loss (MESH:D015431), neuroinflammation (MESH:D000090862), brain inflammation (MESH:D004660), gall bladder (MESH:D005706), CD (MESH:D003424), cancer of the intestine (MESH:D007414), colitis (MESH:D003092), Inflammation (MESH:D007249), rectal bleeding (MESH:D012002), UC (MESH:D003093), IBD (MESH:D015212), bloody diarrhea (MESH:D003967)
- **Chemicals:** pentobarbital (MESH:D010424), water (MESH:D014867), H&amp;E (MESH:D006371), TNBS (MESH:D014302), saline (MESH:D012965), toluene (MESH:D014050), nitrogen (MESH:D009584), NP155 (-), isoflurane (MESH:D007530), O2 (MESH:D010100), glucose (MESH:D005947), PFA (MESH:C003043), Alexa Fluor-488 (MESH:C000711379), Hematoxylin (MESH:D006416), ethanol (MESH:D000431), Tween 20 (MESH:D011136), 11C]PK11195 (MESH:C504060), 18F]FDG (MESH:D019788), Cobalt (MESH:D003035), Eosin-Y (MESH:D004801), sucrose (MESH:D013395), DAPI (MESH:C007293),  (MESH:D016264),  (MESH:D011720),  (MESH:C530129),  (MESH:D011743)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Dipturus trachyderma (ray, species) [taxon 255564]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4544644/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC4544644/full.md

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Source: https://tomesphere.com/paper/PMC4544644