The Role of PET/CT in Detecting Radiation-Induced Cardiovascular Toxicity in Thoracic Cancer Patients

Objectives: Radiation-induced heart disease (RIHD) is an increasingly recognized cause of mortality in patients receiving radiation therapy (RT) for thoracic malignancies such as mediastinal lymphomas, breast, lung, and oesophageal carcinomas. RIHD is a complex disease entity that includes both early and late cardiac complications. These include coronary artery disease, cardiomyopathies, valvular abnormalities, and arrhythmias. Prior studies have shown greater cardiac damage in patients with left-sided thoracic malignancies due to their close proximity to the heart, and rates of RIHD are also related to the dosage and duration of RT. However, no clear guidelines currently exist in regard to optimal screening methods for RIHD. There are still many unknowns regarding the causative biomolecular pathophysiology of RIHD. However, it is thought to be, at least in part, related to the generation of reactive oxygen species that disrupt DNA strands and damage blood vessels, causing myocardial fibrosis. Radiation toxicity mimics spontaneous atherosclerosis and can cause myocardial perfusion abnormalities by means of mitochondrial damage, microvascular injury, myocardial degeneration, and interstitial fibrosis. As such, the use of positron emission tomography / computed tomography (PET/CT) has enormous potential in identifying disease development early. To date, various tracers such as Fluorodeoxyglucose (FDG), Sodium Fluoride (NaF) and 13N-ammonia have been utilized to detect RIHD, each with different strengths and weaknesses. FDG has a predilection to localize in areas of inflammation, whereas NaF tends to localize in calcific plaques. In comparison, 13N-ammonia is utilized to detect myocardial perfusion abnormalities along with global and regional left ventricular dysfunction at an early stage. Additionally, FDG-PET/CT has demonstrated linear uptake in vessel walls for vasculitis, while also showing patchy uptake in atherosclerosis plaques. PET/CT imaging has the potential to play a key role in detecting and diagnosing RIHD in the early and subclinical stages, thus positively influencing long-term clinical outcomes. As RIHD is still a major concern even with normal tissue-sparing, newer radiation techniques such as 3D-conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton therapy, diagnosis of cardiac toxicity can play a significant role in preventing morbidity and mortality in patients undergoing RT. In this scientific communication we will review the following: 1) the potential role of PET/CT in RIHD, 2) the advantages and disadvantages of various radiotracers in detecting RIHD, 3) the use of PET/CT for risk stratification of patients, 4) the effect of tumor location on RIHD risk, and 5) current strategies to minimize radiation exposure to the heart and prevent RIHD