Target identification for the diagnosis and intervention of vulnerable atherosclerotic plaques beyond (18)F-fluorodeoxyglucose positron emission tomography imaging: promising tracers on the horizon

Cardiovascular disease is the major cause of morbidity and mortality in developed countries and atherosclerosis is the major cause of cardiovascular disease. Atherosclerotic lesions obstruct blood flow in the arterial vessel wall and can rupture leading to the formation of occlusive thrombi. Conventional diagnostic tools are still of limited value for identifying the vulnerable arterial plaque and for predicting its risk of rupture and of releasing thromboembolic material. Knowledge of the molecular and biological processes implicated in the process of atherosclerosis will advance the development of imaging probes to differentiate the vulnerable plaque. The development of imaging probes with high sensitivity and specificity in identifying high-risk atherosclerotic vessel wall changes and plaques is crucial for improving knowledge-based decisions and tailored individual interventions. Arterial PET imaging with (18)F-FDG has shown promising results in identifying inflammatory vessel wall changes in numerous studies and clinical trials. However, due to its limited specificity in general and its intense physiological uptake in the left ventricular myocardium that impair imaging of the coronary arteries, different PET tracers for the molecular imaging of atherosclerosis have been evaluated. This review describes biological, chemical and medical expertise supporting a translational approach that will enable the development of new or the evaluation of existing PET tracers for the identification of vulnerable atherosclerotic plaques for better risk prediction and benefit to patients.