REVIEW ARTICLE Nuclear cardiology in the context of multimodality imaging to detect cardiac toxicity from cancer therapeutics: Established and emerging methods Aaron Soufer, MD, a Chi Liu, PhD, b Mariana L. Henry, MPH, BS, a and Lauren A. Baldassarre, MD a a Department of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT b Department of Radiology and Biomedical Engineering, Yale University School of Medicine, New Haven, CT Received Feb 4, 2019; accepted Feb 12, 2019 doi:10.1007/s12350-019-01671-6 The complexity of cancer therapies has vastly expanded in the last decade, along with type and severity of cardiac toxicities associated with these treatments. Prevention of pre-clinical car- diotoxicity may improve cardiovascular outcomes and circumvent the decision to place life- sustaining chemotherapeutic agents on hold, making the early detection of cancer therapeutic related cardiac toxicity with non-invasive imaging essential to the care of these patients. There are several established methods of cardiac imaging in the areas of nuclear cardiology, echocardiography, computed tomography, and cardiac magnetic resonance imaging that are used to assess for cardiovascular toxicity of cancer treatments, with several methods under development. The following review will provide an overview of current and emerging imaging techniques in these areas. (J Nucl Cardiol 2019) Key Words: Multimodality Æ cardiac imaging Æ cardiotoxicity Æ cardio-oncology Æ cancer therapeutics related cardiac dysfunction BACKGROUND Cancer is the second leading cause of death in the United States, with 595,919 cancer related deaths and 1.6 million new cases reported in the year 2015. 1 There has been rapid growth of oncologic therapies, which has revolutionized the care of these patients and improved overall survival. These therapies have become increas- ingly complex, and have unearthed a wide array of cardiovascular toxicities that must be understood by cardiologists in order to optimize the multidisciplinary care of these patients. Agents that are implicated in cardiac toxicity related to cancer therapeutics include— but are not limited to—anthracyclines, HER2 inhibitors, tyrosine kinase inhibitors, alkylating agents, antimetabo- lites, proteasome inhibitors, immune checkpoint inhibitors (CPIs), and mediastinal external beam radia- tion therapy (EBRT). The mechanisms for these toxicities are vast, and may include excess generation of reactive oxygen species (ROS), mitochondrial dys- function, DNA damage, endothelial injury, and vasospasm, which result in myocyte apoptosis or necro- sis, myocardial fibrosis, myocardial ischemia, or myocarditis. 2 This may manifest clinically with car- diomyopathy, arrhythmia, ischemic heart disease, valvular heart disease, or pericardial disease. Although cardiomyopathy induced by anthracycli- nes and HER2 inhibitors has been classically categorized into irreversible and reversible forms of toxicity, 3 respectively, this conceptual construct has Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12350-019-01671-6) contains sup- plementary material, which is available to authorized users. The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarises the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com. Reprint requests: Aaron Soufer, MD, Department of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT; aaron.soufer@yale.edu 1071-3581/$34.00 Copyright Ó 2019 American Society of Nuclear Cardiology.