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

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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2442-2448
Number of pages7
JournalMolecular Medicine Reports
Issue number2
StatePublished - Feb 2018


  • Hydroxyapatite
  • Imaging
  • Inflammation
  • Methotrexate
  • Radiolabeling
  • Rheumatoid arthritis
  • Technetium-99m

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research


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