Search

Doxorubicin (DOX) is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic effects and the lack of methods to detect these at early time points. In the present study, we evaluated if [64Cu]Cu-NODAGA-E[(cRGDyK)]2 positron emission tomography–computed tomography ([64Cu]Cu-RGD PET/CT) could detect cardiotoxicity in a rat model of DOX-induced heart failure. Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg of DOX or left untreated. Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week 8. [64Cu]Cu-RGD PET/CT scans were performed in week 4. DOX treatment led to a decline in pump function as well as an increase in cardiac and thymic uptake of [64Cu]Cu-RGD. In addition, DOX altered cardiac gene expression, led to infiltration of immune cells, reduced endothelial content, and increased interstitial fibrosis. Furthermore, concentrations of inflammatory plasma proteins were increased in the DOX group. In conclusion, DOX treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using [64Cu]Cu-RGD PET/CT at early time points. [64Cu]Cu-RGD uptake in the myocardial septum and thymus predicted a low left ventricular ejection fraction in week 8.

For imaging of atherosclerotic disease, lumenography using computed tomography, ultrasonography, or invasive angiography is still the backbone of evaluation. However, these methods are less effective to predict the likelihood of future thromboembolic events caused by vulnerability of plaques. PET and MR imaging have been used separately with success for plaque characterization. Where MR imaging has the ability to reveal plaque composition, PET has the ability to visualize plaque activity. Together this leads to a comprehensive evaluation of plaque vulnerability. In this review, the authors go through data and arguments that support increased use of PET/MR imaging in atherosclerotic imaging.

Supplemental Digital Content is available in the text.