While liposomes and nanoparticles have been the subject of intense research for more than 40 years, few particles have been translated into clinical practice. Advantages of these particles include the potential to overcome the cardiac, renal or neural toxicity of systemic chemotherapy, the opportunities for multivalent targeting, the gradual yet significant accumulation within tumors due to leaky blood vessels and the myriad of new approaches to locally alter the properties of the particle in the region of interest. Given the complexity of the design and co-optimization of the surface architecture, shell formulation and drug loading, methods to image the pharmacokinetics of nanoparticles in living systems are an essential part of an efficient research methodology. Here, we describe our efforts to label the shell and drug core of lipid-shelled particles with a goal of facilitating translation of activatable particles.