Abstract
Transferrin receptor (TfR) is highly expressed on rapidly dividing inflammatory cells, but not in nonproliferating cells. We investigated whether scintigraphic imaging using 99mTechnetium-radiolabeled transferrin (99mTc–Tf) is useful for early detection of synovial inflammation of collagen-induced arthritis (CIA) mouse. 99mTc–Tf conjugate was synthesized to target the TfR in inflamed synovium. 99mTc–Tf scintigraphic images were obtained in nonarthritic normal mouse and advanced phase of CIA mouse. 99mTc–Tf and 99mTc–methylenediphosphonate (99mTc–MDP) bone scintigraphic images were obtained in same early phase of CIA mouse. Western blot analysis, hematoxylin & eosin (H&E), and immunohistochemical staining were performed to determine development of arthritis and expression of TfR. Image analyses revealed that the uptake of 99mTc–Tf in inflamed joints of advanced phase of CIA mouse was markedly higher than those by normal nonarthritic mouse. 99mTc–Tf scintigraphy also showed higher uptake in knee joint prior to significant joint swelling in early phase of CIA mouse but 99mTc–MDP bone scintigraphy does not. These scintigraphic findings are well correlated with the results of Western blot, H&E and immunohistochemical analysis. In conclusion, TfR can be used as a specific target for molecular imaging in CIA mouse, and 99mTc–Tf scintigraphy detects synovial inflammation prior to significant clinical findings in CIA mouse.
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Abbreviations
- TfR:
-
Transferrin receptor
- 99mTc–Tf:
-
99mTechnetium-radiolabeled transferrin
- CIA:
-
Collagen-induced arthritis
- 99mTc–MDP:
-
99mTc–methylenediphosphonate
- H&E:
-
Hematoxylin & eosin
- RA:
-
Rheumatoid arthritis
- HYNIC:
-
Hydrazino nicotinate hydrochloride
- ABC:
-
Avidin/biotin peroxidase complex
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This work was supported by grant of the Nuclear Energy Research and Development Program (2008-00285) from the Ministry of Science and Technology of Korea.
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Sang-Il Lee and Eun-Mi Kim contributed equally to this work.
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Lee, SI., Kim, EM., Kim, S.L. et al. Molecular scintigraphic imaging using 99mTc–transferrin is useful for early detection of synovial inflammation of collagen-induced arthritis mouse. Rheumatol Int 29, 153–157 (2008). https://doi.org/10.1007/s00296-008-0655-z
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DOI: https://doi.org/10.1007/s00296-008-0655-z