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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/626570 |
| Date | 27 November 2017 |
| Creators | Papachristou, Maria, Kastis, George, Stavrou, Petros, Xanthopoulos, Stavros, Furenlid, Lars, Datseris, Ioannis, Bouziotis, Penelope |
| Contributors | 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, Department of Nuclear Medicine‑PET/CT, General Hospital of Athens ‘Evaggelismos’, 10676 Athens, Greece, Institute for Nuclear and Radiological Sciences and Technology, Energy and Safety, National Center for Scientific Research ‘Demokritos’, 15310 Athens, Greece, Center for Gamma‑Ray Imaging, Department of Medical Imaging, University of Arizona, Tucson, AZ 85724, USA, Department of Nuclear Medicine‑PET/CT, General Hospital of Athens ‘Evaggelismos’, 10676 Athens, Greece, Institute for Nuclear and Radiological Sciences and Technology, Energy and Safety, National Center for Scientific Research ‘Demokritos’, 15310 Athens, Greece |
| Publisher | SPANDIDOS PUBL LTD |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © Papachristou et al. This is an open access article distributed under the terms of Creative Commons Attribution License. |
| Relation | http://www.spandidos-publications.com/10.3892/mmr.2017.8166 |
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