(99m)Tc-annexin V and (111)In-antimyosin antibody uptake in experimental myocardial infarction in rats.
OBJECTIVE
(99m)Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ((111)In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain).


METHODS
The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats.


RESULTS
All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1+/-0.6 versus 1.5+/-0.3 (p=0.001) for ANX and 1.99+/-0.44 versus 1.01+/-0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6+/-0.9 versus 5.0+/-1.8 at 24 h), while Apostain staining was very low (0.06+/-0.06% of cells).


CONCLUSIONS
In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas.
Sarda-Mantel
Laure
L
EA 3512, Nuclear Medicine Department, Bichat Hospital AP-HP, Paris, France. sarda@bichat.inserm.fr
Michel
Jean-Baptiste
JB
Rouzet
François
F
Martet
Geneviève
G
Louedec
Liliane
L
Vanderheyden
Jean-Luc
JL
Hervatin
Florence
F
Raguin
Olivier
O
Vrigneaud
Jean-Marc
JM
Khaw
Ban An
BA
Le Guludec
Dominique
D
D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics*; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D017209:Apoptosis; D006321:Heart / Q000000981:diagnostic imaging; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009218:Myosins / Q000276:immunology / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C417036:technetium Tc 99m annexin V; D009218:Myosins