Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A proof-of-concept study
AffiliationUniv Arizona, Dept Med Imaging, Ctr Gamma Ray Imaging
MetadataShow full item record
PublisherSPANDIDOS PUBL LTD
CitationRadiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A proof-of-concept study 2017 Molecular Medicine Reports
JournalMolecular Medicine Reports
Rights© Papachristou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractMethotrexate (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.
Note6 month embargo; Published online: 27 November 2017
VersionFinal published version
SponsorsNational Institutes of Health/National Institute of Biomedical Imaging and Bioengineering [P41-EB002035]; Onassis Scholars' Association of the 'Alexander S. Onassis' Public Benefit Foundation
- Characterization of 99mTc-labeled cytokine ligands for inflammation imaging via TNF and IL-1 pathways.
- Authors: Liu Z, Wyffels L, Barber C, Wan L, Xu H, Hui MM, Furenlid LR, Woolfenden JM
- Issue date: 2012 Oct
- Identification and characterization of the direct interaction between methotrexate (MTX) and high-mobility group box 1 (HMGB1) protein.
- Authors: Kuroiwa Y, Takakusagi Y, Kusayanagi T, Kuramochi K, Imai T, Hirayama T, Ito I, Yoshida M, Sakaguchi K, Sugawara F
- Issue date: 2013
- Methotrexate (MTX)-cIBR conjugate for targeting MTX to leukocytes: conjugate stability and in vivo efficacy in suppressing rheumatoid arthritis.
- Authors: Majumdar S, Anderson ME, Xu CR, Yakovleva TV, Gu LC, Malefyt TR, Siahaan TJ
- Issue date: 2012 Sep
- (99m)Tc human IgG radiolabelled by HYNIC. Biodistribution and scintigraphy of experimentally induced inflammatory lesions in animal model.
- Authors: Karczmarczyk U, Markiewicz A, Mikołajczak R, Lisiak E, Bilski M, Pietrzykowski J, Michalik J
- Issue date: 2004
- 99mTc-HYNIC-spermine for imaging polyamine transport system-positive tumours: preclinical evaluation.
- Authors: Pesnel S, Guminski Y, Pillon A, Lerondel S, Imbert T, Guilbaud N, Kruczynski A, Bailly C, Le Pape A
- Issue date: 2011 Oct