99mTc-Hynic-annexin V imaging to evaluate inflammation and apoptosis in rats with autoimmune myocarditis.
Inflammation and cell death are two important components of myocarditis. We evaluated the distribution of inflammation and apoptotic cell death in rats with autoimmune myocarditis using two radiotracers - technetium-99m Hynic-annexin V ((99m)Tc-annexin) as a marker of apoptotic cell death and carbon-14 deoxyglucose ((14)C-DG) as a marker of inflammation - in comparison with histologic findings. Three, 7 and 14 weeks after immunization with porcine cardiac myosin (acute, subacute, and chronic phases, respectively) (99m)Tc-annexin and (14)C-DG were injected. The uptake in the total heart was determined as the percentage of injected dose per gram (% ID/g) by tissue counting. Dual-tracer autoradiography with (99m)Tc-annexin and (14)C-DG was performed. The distribution of each of these agents was compared with the results of hematoxylin and eosin staining to identify areas of inflammation, and TUNEL staining to identify areas of apoptosis. Total cardiac uptake of (99m)Tc-annexin in the acute phase of myocarditis was significantly higher than that in normal rats (1.28%+/-0.30% vs 0.46%+/-0.01%; P<0.0001); it then decreased in the subacute phase and reached normal levels (0.56%+/-0.08% vs 0.60%+/-0.08%; P=NS). Total cardiac uptake of (14)C-DG in the acute phase of myocarditis was significantly higher than that in normal rats (2.78%+/-0.95% vs 1.02%+/-0.25%; P<0.0001); it then decreased in the subacute phase, but still remained higher than in controls (2.06%+/-0.52% vs 1.37%+/-0.46%; P<0.05). Using autoradiography and staining of tissue specimens, it was found that most histologic inflammatory foci corresponded to areas of high (14)C-DG uptake; some also corresponded to areas of high (99m)Tc-annexin uptake in the acute phase of myocarditis. (99m)Tc-annexin localization was strongly correlated with the number of TUNEL-positive cells (P<0.0001, r=0.83), but the uptake of (14)C-DG showed no relationship with it. There is a marked difference in the distribution of inflammation and apoptotic cell death in the myocardium of animals with immune myocarditis. These changes are mirrored by the localization of (14)C-DG and (99m)Tc-annexin. Sites of inflammation and zones of apoptotic cell death change over the course of immune myocarditis.
Tokita
Naoki
N
Department of Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara-city, Kanagawa 228-8555, Japan. tokita@med.kitasato-u.ac.jp
Hasegawa
Shinji
S
Maruyama
Kaoru
K
Izumi
Tohru
T
Blankenberg
Francis G
FG
Tait
Jonathan F
JF
Strauss
H William
HW
Nishimura
Tsunehiko
T
D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D024722:Cardiac Myosins; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D006321:Heart / Q000000981:diagnostic imaging; D008297:Male; D009205:Myocarditis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D014018:Tissue Distribution
D017304:Annexin A5; D002250:Carbon Radioisotopes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C417036:technetium Tc 99m annexin V; D003847:Deoxyglucose; D024722:Cardiac Myosins