Cardiovascular Immunotherapy and the Role of Imaging.

Abstract

Despite significant advances in prevention and treatment, cardiovascular diseases (CVDs) remain the most common cause of death in the United States.1–3 In part, and compared with treatment developments in oncology, this is because of the lack of current generation CVD precision therapies.4–6 Most CVDs are caused by atherosclerosis, a disease process that causes thickening of the arterial wall because of inflammation and lipid accumulation, resulting in plaque formation.7,8 Macrophage dynamics plays a central role in atherosclerosis progression, vessel wall destabilization, and—as has been recently discovered—plaque aggravation because of myocardial infarction.9–11 Therefore, and despite current standardized treatments, ≈25% of patients who had myocardial infarction or stroke will experience secondary major adverse cardiovascular events, often more harmful than the primary event.12–14 To break this vicious cycle, innovative and tailored therapeutic strategies are needed. Various targeted immunotherapies that showed anticancer potential in in vitro screens also displayed in vivo potential in mouse models. Such proof-of-concept studies in validated syngeneic mouse tumor models not only provide information on in vivo efficacy but also disclose the targeted immunotherapies’ underlying mechanism of action and safety profile. However, immunotherapies’ high costs and the identification of amendable patients compromise clinical translation.15,16 Continued and focused efforts are needed to understand patient responsiveness and reduce high dropout rates in trials. A parallel effort focused on the development of novel imaging tools that can guide patient selection may offer a potential solution. Positron emission tomography (PET) can be used to trace immunotherapies. So-called immunoPET uses antibodies, developed for cancer treatment, that selectively recognize a specific epitope on target cells. The antibodies are labeled with radioactive isotopes, such as zirconium-89 or iodine-124, with relatively long decay half-lives of 3.27 and 4.18 days, respectively, to …