**6. Apoptosis imaging in cardiotoxicity induced by chemotherapy**

The development of chemotherapy has played a significant role in the management of cancer patients. Of the classic cytotoxic agents, antracyclines are the still one of the most important agents for cancer therapy and are well known for their dose dependent acute and chronic cardiotoxicity, resulting in irreversible and progressive cardiac dysfunction and heart failure. Although new anticancer molecular targeting agents improved the prognosis of cancer patients, some agents may have serious cardiovascular side effect. Standard clinical approaches utilize the serial monitoring of the left ventricular ejection fraction to identify chemotherapy induced cardiotoxicity. For this purpose, radionuclide ECG gated blood-pool scintigraphy has been used as a gold standard technique. However, ejection fraction impairment is relatively late manifestation of myocardial damage. Therefore, the development of more sensitive methods is required to identify the cardiotoxicity before the onset of ventricular dysfunction.

In a rat model of doxorubicin cardiotoxicity (cumulative dose: 7.5mg/Kg, 10mg/Kg, 12.5mg/Kg), planar scintigraphy detected the increase of 99mTc-annexin V uptake dose dependently and correlated with expression of left ventricular atrial natriuretic factor messenger RNA (Bennink, et al., 2004). Another study with doxorubicin treated rats (cumulative dose: 7.5mg/Kg and 15mg/Kg) demonstrated that dose dependent increase in 99mTc-annexin V uptake by SPECT/CT and TUNEL positivity. In contrast in this syudy, echocardiography detected ventricular dysfunction only at the highest doxorubicin dose ( Gabrielson, et al., 2008). These data suggest that apoptosis imaging could serve as a more sensitive early marker of doxorubicin cardiotoxixity than left ventricular dysfunction, might providing the opportunity to modify or stop the chemotherapy before clinically overt heart failure.
