Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A proof-of-concept study

Papachristou,Maria; Kastis,George A.; Stavrou,Petros  Z.; Xanthopoulos,Stavros; Furenlid,Lars  R.; Datseris,Ioannis  E.; Bouziotis,Penelope

doi:10.3892/mmr.2017.8166

Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A proof-of-concept study

Authors:
- Maria Papachristou
- George A. Kastis
- Petros Z. Stavrou
- Stavros Xanthopoulos
- Lars R. Furenlid
- Ioannis E. Datseris
- Penelope Bouziotis
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Affiliations: Department of Nuclear Medicine‑PET/CT, General Hospital of Athens ‘Evaggelismos’, 10676 Athens, Greece, Research Center of Mathematics, Academy of Athens, 11527 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
Published online on: November 27, 2017 https://doi.org/10.3892/mmr.2017.8166
Pages: 2442-2448
Copyright: © Papachristou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 (99mTc‑MTX) as a radiotracer was investigated for the identification of inflammatory target sites. The labelling of MTX was carried out via a 99mTc‑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 99mTc, 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 ~50% at 4 h. These preclinical ex vivo and in vivo studies indicated that 99mTc‑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 99mTc‑MTX as a radiotracer for inflammation associated with rheumatoid arthritis.

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