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Imaging of (sub)clinical arthritis by targeting the translocator protein (TSPO) on activated macrophages is feasible using<jats:italic>(R)-<\/jats:italic>[<jats:sup>11<\/jats:sup>C] PK11195-based positron emission tomography (PET), but clinical applications are limited by background uptake in peri-articular bone\/bone marrow. The purpose of the present study was to evaluate two other TSPO ligands with potentially lower background uptake in neurological studies, [<jats:sup>11<\/jats:sup>C]DPA-713 and [<jats:sup>18<\/jats:sup>F]DPA-714, in a rat model of arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>TSPO binding of DPA-713, DPA-714 and PK11195 were assessed by<jats:italic>in vitro<\/jats:italic>competition studies with [<jats:sup>3<\/jats:sup>H]DPA-713 using human macrophage THP-1 cells and CD14<jats:sup>+<\/jats:sup>monocytes from healthy volunteers.<jats:italic>In vivo<\/jats:italic>studies were performed in rats with methylated bovine serum albumin-induced knee arthritis. Immunohistochemistry with anti-TSPO antibody was performed on paraffin-embedded sections. Rats were imaged with [<jats:sup>11<\/jats:sup>C]DPA-713 or [<jats:sup>18<\/jats:sup>F]DPA-714 PET, followed by<jats:italic>ex vivo<\/jats:italic>tissue distribution studies. Results were compared with those obtained with the tracer<jats:italic>(R)-<\/jats:italic>[<jats:sup>11<\/jats:sup>C]PK11195, the established ligand for TSPO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In THP-1 cells, relative TSPO binding of DPA-713 and DPA-714 were 7-fold and 25-fold higher, respectively, than in PK11195. Comparable results were observed in CD14<jats:sup>+<\/jats:sup>monocytes from healthy volunteers. In the arthritis rat model, immunohistochemistry confirmed the presence of TSPO-positive inflammatory cells in the arthritic knee. PET images showed that uptake of [<jats:sup>11<\/jats:sup>C]DPA-713 and [<jats:sup>18<\/jats:sup>F]DPA-714 in arthritic knees was significantly increased compared with contralateral knees and knees of normal rats. Uptake in arthritic knees could be largely blocked by an excess of PK11195. [<jats:sup>11<\/jats:sup>C]DPA-713 and [<jats:sup>18<\/jats:sup>F]DPA-714 provided improved contrast compared with<jats:italic>(R)<\/jats:italic>-[<jats:sup>11<\/jats:sup>C]PK11195, as was shown by significantly higher arthritic knee-to-bone ratios of [<jats:sup>11<\/jats:sup>C]DPA-713 (1.60\u2009\u00b1\u20090.31) and [<jats:sup>18<\/jats:sup>F]DPA-714 (1.55\u2009\u00b1\u20090.10) compared with<jats:italic>(R)<\/jats:italic>-[<jats:sup>11<\/jats:sup>C]PK11195 (1.14\u2009\u00b1\u20090.19).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>[<jats:sup>11<\/jats:sup>C]DPA-713 and [<jats:sup>18<\/jats:sup>F]DPA-714 clearly visualized arthritis and exhibited lower (peri-articular) bone\/bone marrow uptake than<jats:italic>(R)-<\/jats:italic>[<jats:sup>11<\/jats:sup>C]PK11195. These features merit further investigation of these tracers for early diagnosis and therapy monitoring of RA in a clinical setting.<\/jats:p><\/jats:sec>","DOI":"10.1186\/ar4509","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T10:01:46Z","timestamp":1394791306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis"],"prefix":"10.1186","volume":"16","author":[{"given":"Yoony YJ","family":"Gent","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Weijers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla FM","family":"Molthoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert D","family":"Windhorst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc C","family":"Huisman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kassiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerrit","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriaan A","family":"Lammertsma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conny J","family":"van der Laken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,3,14]]},"reference":[{"key":"4155_CR1","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1056\/NEJMra1004965","volume":"365","author":"IB McInnes","year":"2011","unstructured":"McInnes IB, Schett G: The pathogenesis of rheumatoid arthritis. 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