Mechanisms underlying atherosclerotic plaque rupture are complex and unpredictable by any current imaging test. However, several key pathogenic processes known to increase the likelihood of an acute plaque event can be tracked in vivo using positron emission tomography (PET). In this issue of Heart, Jenkins et al.[1] examine the utility of 18F-fluciclatide, an v3integrin binding PET tracer, for imaging atherosclerosis. This intriguing study adds great momentum in the push to identify novel methods for imaging molecular signatures of high-risk plaques, and raises several important broader considerations for the field.