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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85039716284&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039716284&partnerID=8YFLogxK
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 -