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Journal of Nuclear Medicine Vol. 45 No. 6 1081-1086
© 2004 by Society of Nuclear Medicine


Basic Science Investigations

Imaging Apoptosis with 99mTc-Annexin-V in Experimental Subacute Myocarditis

Can Peker, MD1, Laure Sarda-Mantel, MD1, Paule Loiseau1, François Rouzet, MD1, Lubna Nazneen1, Geneviève Martet1, Jean-Marc Vrigneaud, PhD1, Alain Meulemans, PhD1, Georges Saumon, MD1, Jean-Baptiste Michel, MD, PhD2 and Dominique Le Guludec, MD, PhD1

1 Équipe d’Accueil 35 12, Faculté Bichat-Claude Bernard et Service de Médecine Nucléaire de l’hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
2 Institut National de la Santé et de la Recherche Médicale, Unité 460, Unité de Formation et de Recherche Bichat, Paris, France

99mTc-Annexin-V (ANX), which allows in vivo detection of apoptotic cells, is potentially a promising noninvasive tool to diagnose myocarditis. To test this assumption, we compared the myocardial uptake of ANX (imaging and quantitative autoradiography) in experimental subacute myocarditis (Wistar Bonn/Kobori rats [WBN/Kob]) and in normal Wistar rats. WBN/Kob is an inbred strain of Wistar rat in which myocardial injury mimicking subacute catecholamine-induced myocarditis spontaneously develops (course duration, 18 mo). The apoptotic myocardial rates were determined by immunohistochemical studies. Methods: Fourteen WBN/Kob rats (8–10 mo old) and 12 control rats were injected with ANX (7.4 MBq/100 g). Ten-minute anterior planar thoracic images (matrix, 128 x 128) were obtained using a pinhole collimator, 1 and 4 h after injection. Heart-to-lung activity ratios were calculated on the scintigrams. Four hours after ANX injection, quantitative autoradiography of myocardial slices was performed, as well as histologic studies with hematoxylin–eosin and with a staining assay specific for apoptotic cells. Results: Heart-to-lung activity ratios were higher in WBN/Kob rats than in control rats on 4-h images (2.07 ± 0.07 vs. 1.66 ± 0.06, P = 0.0007). Autoradiographic studies showed moderate diffuse, homogeneous myocardial ANX uptake significantly higher in WBN/Kob rats than in control rats: 54 ± 4 versus 37 ± 3 counts/mm2 (P < 0.007). The apoptotic rate, evaluated with an apoptotic cell–staining assay, was 0.51% ± 0.14% of cells in WBN/Kob rats versus 0.0042% ± 0.0008% in control rats (P < 0.008). Conclusion: Compared with control rats, rats with subacute myocarditis mimicking catecholamine-induced myocarditis showed increased ANX myocardial uptake. This suggests a potential role for ANX imaging in the diagnosis of myocarditis.

Key Words: apoptosis • 99mTc-annexin-V • myocarditis




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