Imaging apoptosis with (99m)Tc-annexin-V in experimental subacute myocarditis.
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/mm(2) (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).


CONCLUSIONS
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.
Peker
Can
C
Equipe d'Accueil 35 12, Faculté Bichat-Claude Bernard et Service de Médecine Nucléaire de l'hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France.
Sarda-Mantel
Laure
L
Loiseau
Paule
P
Rouzet
François
F
Nazneen
Lubna
L
Martet
Geneviève
G
Vrigneaud
Jean-Marc
JM
Meulemans
Alain
A
Saumon
Georges
G
Michel
Jean-Baptiste
JB
Le Guludec
Dominique
D
D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics*; D017209:Apoptosis; D004195:Disease Models, Animal; D006321:Heart / Q000000981:diagnostic imaging*; D008297:Male; D009205:Myocarditis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D017304:Annexin A5; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C417036:technetium Tc 99m annexin V