**5. Apoptosis imaging in myocarditis**

In a rat model of autoimmune myocarditis, 99mTc-annexin V (HYNIC annexin V) and 14Cdeoxyglucose (DG) uptakes were examined (Tokita, et al.,2003). Myocarditis was triggered by an immunization of rats by infusing porcine cardiac myosine and the rats formed antibodies against the myosin and developed myocarditis. In acute phase of myocarditis, both 99mTc-annexin V (2.8 time more than normal rats) and 14C-DG (2.7 time more than normal rats) uptake increased significantly, however, only 99mTc-annexin V distribution correlated with the TUNEL positive area, and the distribution of 14C-DG correlated with inflammatory cell infiltration. In subacute phase, 99mTc-annexin V uptake returned normal level, on the other hand, 14C-DG uptake decreased but still higher uptake reflecting prolonged mild inflammatory cell infiltration. In this model of immune myocarditis, there was a marked difference in distribution of apoptotic cell death and inflammation. The data indicates that 99mTc-annexin V uptake is specific in myocardial apoptotic process induced by inflammation and is independent of inflammatory cell infiltration.

Another animal experiment in a rat model that develops spontaneous myocarditis mimicking catecholamine induced subacute myocarditis demonstrated significantly increased 99mTc-annexin V uptake in planar scinitgraphy. Autoradiogrpahy confirmed increased 99mTc-annexin V uptake. Histopatology demonstrated patchy areas of interstitial edema with inflammatory cells in the perivascular areas and at cardiocyte layers, and myocyte necrosis with nuclear extrusion, scattered throughout the myocardium and apostatin-positive cells were diffusely but inhomogeneously distributed throughout the myocardium (Peker, et al., 2004).

In myocarditis, apoptosis imaging might play an important role, in confirming the diagnosis in terms of the extent of the involvement and disease activity, selecting patients with antiapoptotic therapy and monitoring the effect of therapy.

Apoptosis Imaging in Diseased Myocardium 261

patients with moderate acute rejection by endomyocardial biopsy showed significant 99mTcannexin V uptake, however, specificity was suboptimal with 4 of 8 patients without rejection

All these animal and clinical studies revealed that the apoptosis imaging has potential to noninvasively identify patients with transplant rejection and monitor the response to

For the imaging apoptosis, for the time being, it appears that agents that bind to markers expressing cell surface of apoptotic cells, such as annexin V and its derivatives, have advantage in terms of the sensitivity and specificity over other tracers. Based on the research achievement to date including experiences with 99mTc-annexin V imaging in patients, 99mTcannexin V and its related tracers are considered as one of the most suitable tracers for clinical application at this stage, and also the positron labeled tracers such as 18F-annexin V are desired to apply clinical imaging. In cardiac diseases that involve cardiomyocytes, myocytes loss implies loss of cardiac function because cardiomyctes cannot be regenerated through cell division. In acute coronary syndrome, measurement of cardiac biomarkers are standard diagnostic tool, but they reflect the results of cardiomyocytes death. Whereas, apoptosis imaging such as 99mTc-annexin V can identify the cells starting or undergoing apoptosis, however, part of PS exposure of these cells might be reversible and some cells are capable of surviving. Therefore, apoptosis imaging might be beneficial for future strategy of the patient's management. Other than acute coronary syndrome, including heart failure, myocarditis, cardiomyopathies, and transplanted rejection, apoptotic cell death has turned out one of the crucial players in underlying pathophysiologies. Hence, apoptosis imaging in patients with various cardiac diseases will enhance the understanding of the ongoing pathophysiology, identification of high risk patients, and lead to effective therapies to

salvage the myocardium in risk and be helpful in monitoring the effect of therapy.

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inhibition ameliorates apoptosis, reduces myocardial troponin-I cleavage, protects

demonstrating significant 99mTc-annexin V uptake.

immune modulation therapy.

**8. Conclusions** 

**9. References** 
