In vivo detection of cell death in the area at risk in acute myocardial infarction.
Annexin A5 is a phospholipid binding protein with high affinity for phosphatidyl-serine, which is externalized by cells undergoing programmed cell death. An increased programmed cell death rate has been reported in the heart after myocardial infarction (MI). The aim of this study was to correctly localize annexin A5 uptake in vivo and to determine the area at risk in humans with acute MI.


METHODS
Nine patients were studied. Before reperfusion was achieved, (99m)Tc-sestamibi was injected intravenously. Myocardial (99m)Tc-sestamibi perfusion scintigraphy was performed after reperfusion. Thereafter, (99m)Tc-labeled annexin A5 was administered intravenously, followed by scintigraphic imaging of the heart. Myocardial (99m)Tc-sestamibi scintigraphy was repeated 1-3 wk after the MI onset. (99m)Tc-Annexin uptake was also studied in the subacute phase of the MI in 2 patients.


RESULTS
All patients clearly showed perfusion defects on (99m)Tc-sestamibi scintigraphy in concordance with the infarct location. Furthermore, all patients showed accumulation of (99m)Tc-annexin A5 at the infarct site, indicating that cardiomyocytes with externalized phosphatidyl-serine are present in the infarct area. (99m)Tc-sestamibi defects determined 1-3 wk after the MI onset were significantly smaller than the defects in the acute phase. (99m)Tc-annexin uptake was absent in the 2 patients studied in the subacute phase.


CONCLUSIONS
In acute MI, an increase of programmed cell death can be correctly localized in vivo in the area at risk. Furthermore, the decrease in (99m)Tc-sestamibi defect size in the subacute phase of the MI further suggests that in parts of the area at risk, reversible myocardial damage rather than necrosis is present in cardiomyocytes.
Thimister
Paul W L
PW
Department of Nuclear Medicine, University Hospital Maastricht, Maastricht, The Netherlands. p.thimister@orbisconcern.nl
Hofstra
Leo
L
Liem
Ing Han
IH
Boersma
Hendrikus H
HH
Kemerink
Gerrit
G
Reutelingsperger
Chris P M
CP
Heidendal
Guido A K
GA
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D017304:Annexin A5; D017302:Annexins / Q000378:metabolism*; D017209:Apoptosis; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D015609:Organotechnetium Compounds; D010718:Phosphatidylserines / Q000378:metabolism; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon
D017304:Annexin A5; D017302:Annexins; D015609:Organotechnetium Compounds; D010718:Phosphatidylserines; D019275:Radiopharmaceuticals; C447942:technetium Tc 99m BTAP-annexin-V; D017256:Technetium Tc 99m Sestamibi