TY - JOUR
T1 - Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites
T2 - A proof-of-concept study
AU - Papachristou, Maria
AU - Kastis, George A.
AU - Stavrou, Petros Z.
AU - Xanthopoulos, Stavros
AU - Furenlid, Lars R.
AU - Datseris, Ioannis E.
AU - Bouziotis, Penelope
N1 - Funding Information:
The publication of this article was funded by the Onassis Scholars' Association of the ‘Alexander S. Onassis’ Public Benefit Foundation. Dr L. Furenlid was partially supported by The National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering (grant no. P41-EB002035).
Publisher Copyright:
Copyright © 2017 Spandidos Publications. All rights reserved.
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
KW - Hydroxyapatite
KW - Imaging
KW - Inflammation
KW - Methotrexate
KW - Radiolabeling
KW - Rheumatoid arthritis
KW - Technetium-99m
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U2 - 10.3892/mmr.2017.8166
DO - 10.3892/mmr.2017.8166
M3 - Article
C2 - 29207127
AN - SCOPUS:85039716284
SN - 1791-2997
VL - 17
SP - 2442
EP - 2448
JO - Molecular Medicine Reports
JF - Molecular Medicine Reports
IS - 2
ER -