Multimodality PET/MR imaging agents targeted to activated macrophages

The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles (IONPs) have become a popular platform for the fabrication of PET/MRI probes due to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this paper, we report the synthesis of dextran coated iron oxide nanoparticles labeled with the positron emitter 64Cu to generate a PET/MRI probe, and modified with small molecular maleic anhydride to increase negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-64CuDOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand-receptor found on activated macrophages but not on normal vessel walls. MDIO-64Cu-DOTA has an average iron oxide core size of 7-8 nm, an average hydrodynamic diameter of 62.7 nm, an r1 relaxivity of 16.8 mM−1·s−1, and an r2 relaxivity of 83.9 mM−1·s−1 (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the non-modified analog, the accumulation of maleylated DIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-64Cu-DOTA for identification of vulnerable atherosclerotic plaques (VAP) via the targeting of macrophages.