Molecular scintigraphic imaging using Tc-99m-transferrin is useful for early detection of synovial inflammation of collagen-induced arthritis mouse

Abstract

Transferrin receptor (TfR) is highly expressed on rapidly dividing inflammatory cells, but not in nonproliferating cells. We investigated whether scintigraphic imaging using (99m)Technetium-radiolabeled transferrin (Tc-99m-Tf) is useful for early detection of synovial inflammation of collagen-induced arthritis (CIA) mouse. Tc-99m-Tf conjugate was synthesized to target the TfR in inflamed synovium. Tc-99m-Tf scintigraphic images were obtained in nonarthritic normal mouse and advanced phase of CIA mouse. Tc-99m-Tf and Tc-99m-methylenediphosphonate (Tc-99m-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 Tc-99m-Tf in inflamed joints of advanced phase of CIA mouse was markedly higher than those by normal nonarthritic mouse. Tc-99m-Tf scintigraphy also showed higher uptake in knee joint prior to significant joint swelling in early phase of CIA mouse but Tc-99m-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 Tc-99m-Tf scintigraphy detects synovial inflammation prior to significant clinical findings in CIA mouse.