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Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A proof-of-concept studyPapachristou, Maria; Kastis, George; Stavrou, Petros; Xanthopoulos, Stavros; Furenlid, Lars; Datseris, Ioannis; Bouziotis, Penelope; Univ Arizona, Dept Med Imaging, Ctr Gamma Ray Imaging; Department of Nuclear Medicine‑PET/CT, General Hospital of Athens ‘Evaggelismos’, 10676 Athens, Greece; Research Center of Mathematics, Academy of Athens, 11527 Athens, Greece; et al. (SPANDIDOS PUBL LTD, 2017-11-27)Methotrexate (MTX), as a pharmaceutical, is frequently used in tumor chemotherapy and is also a part of the established treatment of a number of autoimmune inflammatory disorders. Radiolabeled MTX has been studied as a tumor-diagnostic agent in a number of published studies. In the present study, the potential use of technetium-99m-labelled MTX (Tc-99m-MTX) as a radiotracer was investigated for the identification of inflammatory target sites. The labelling of MTX was carried out via a Tc-99m-gluconate precursor. Evaluation studies included in vitro stability, plasma protein binding assessment, partition-coefficient estimation, in vivo scintigraphic imaging and ex vivo animal experiments in an animal inflammation model. MTX was successfully labelled with Tc-99m, with a radiochemical purity of >95%. Stability was assessed in plasma, where it remained intact up to 85% at 4 h post-incubation, while protein binding of the radiotracer was observed to be similar to 50% at 4 h. These preclinical ex vivo and in vivo studies indicated that Tc-99m-MTX accumulates in inflamed tissue, as well as in the spinal cord, joints and bones; all areas with relatively high remodeling activity. The results are promising, and set the stage for further work on the development and application of Tc-99m-MTX as a radiotracer for inflammation associated with rheumatoid arthritis.