Published Online
on August 19, 2002

A more recent version of this article appeared on September 10, 2002

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Submitted on March 22, 2002
Revised on June 12, 2002
Accepted on June 12, 2002

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, and 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.

^* To whom correspondence should be addressed. E-mail: yoshi{at}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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