New biomedical strategies are being developed to improve disease detection, therapeutic monitoring, and treatment efficacy in several contexts for example in anti-angiogenic chemotherapy, and prevention of cardiovascular disorders. The use of contrast agents to improve the sensitivity and resolution of diagnostic imaging modalities, detect lesions or organs, and evaluate organ function was immediately recognized. In the last years, superparamagnetic iron oxide (SPIO) nanoparticles have been clinically used as MRI contrast agents for the diagnosis of liver diseases, due to their ability to shorten T2* relaxation times. After the intravenous administration, SPIO nanoparticles are rapidly eliminated from the bloodstream since they are selectively taken up by the Kupffer cells in the liver, spleen, and bone marrow thus improving the clinical tumor detection in these tissues. However, for the investigation of vascular system including functional cardiac diagnosis, angiography and cardiac wall motion assessment, contrast agents with long blood circulation time would be necessary. In fact, imaging applications for long-term monitoring require the repeated administration of SPIO bolus injections, which complicates quantitative comparisons due to the temporal variations in concentration. In this context, researchers have developed several SPIO delivery systems based on red blood cells (RBCs) used as carriers to increase the blood circulation time of contrast agents. Encapsulation of SPIOs into RBCs appears the most attractive strategy to obtain magnetic RBC-constructs suitable for MRI and MPI analyses of blood vascular system.