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Circulation. 2002;106:1397-1402
Published online before print August 19, 2002, doi: 10.1161/01.CIR.0000027823.07104.86
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(Circulation. 2002;106:1397.)
© 2002 American Heart Association, Inc.


Basic Science Reports

Detection of Experimental Autoimmune Myocarditis in Rats by 111In Monoclonal Antibody Specific for Tenascin-C

Mikio Sato, MD; Tetsuya Toyozaki, MD; Kenichi Odaka, MD; Tomoya Uehara, MS; Yasushi Arano, PhD; Hiroshi Hasegawa, MD; Katsuya Yoshida, MD; Kyoko Imanaka-Yoshida, MD; Toshimichi Yoshida, MD; Michiaki Hiroe, MD; Hiroyuki Tadokoro, MD; Toshiaki Irie, PhD; Shuji Tanada, MD; Issei Komuro, MD

From the Department of Cardiovascular Science and Medicine (M.S., K.O., K.Y., I.K., H.H.), the Department of Basic Pathology (T.T), Graduate School of Medicine, and the Department of Molecular Imaging and Radiotherapy (T.U., Y.A.), Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan; the Department of Pathology (K.I.-Y., T.Y.), Mie University School of Medicine, Tsu, Japan; the Cardiology Division (M.H.), International Medical Center of Japan, Tokyo; and the Division of Medical Imaging (H.T., T.I., S.T.), National Institute of Radiological Sciences, Chiba, Japan.

Correspondence to Katsuya Yoshida, MD, Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan. E-mail yoshi@ med.m.chiba-u.ac.jp

Background— Although the identification of inflammatory infiltrates in endomyocardial biopsy specimens is necessary for the definite diagnosis of myocarditis, the biopsy test is invasive and is not sensitive. Therefore, a new diagnostic technique for the early and noninvasive evaluation of myocarditis has been awaited. Expression of tenascin-C (TNC), one of the oligometric extracellular glycoproteins, is induced in various pathological states, including inflammation, suggesting that TNC can be a molecular marker of myocarditis.

Methods and Results— An 111In anti-TNC monoclonal antibody Fab' fragment was injected intravenously into rats with experimental autoimmune myocarditis (EAM), and the biodistribution of this radiotracer was measured. Rapid clearance of radioactivity from the blood was observed in both EAM and control rats (<1% at 6 hours after injection). Myocardial uptake of the tracer was much higher in EAM rats than in control rats (7.54-, 4.39-, and 3.51-fold at 6, 24, and 48 hours after injection, respectively). By autoradiography, high radioactivities were clearly observed in the regions indicative of inflammation in EAM rats. Single-photon emission CT imaging demonstrated the focal myocardial uptake of 111In anti-TNC Fab' in vivo.

Conclusions— Radiolabeled anti-TNC Fab' may be useful for the noninvasive diagnosis of myocarditis.


Key Words: myocarditis • antibodies • nuclear medicine




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