Design and synthesis of calcium responsive magnetic resonance imaging agent: Its relaxation and luminescence studies

Abstract Calcium concentration modulation both inside and outside cell is of considerable interest for nervous system function in normal and pathological conditions. MRI has potential for very high spatial resolution at molecular/cellular level. Design, synthesis and evaluation of Gd-DO3A-AME-NPHE, a calcium responsive MRI contrast agent is presented. The probe is comprised of a Gd 3+ -DO3A core coupled to iminoacetate coordinating groups for calcium induced relaxivity switching. In the absence of Ca 2+ ions, inner sphere water binding to the Gd-DO3A-AME-NPHE is restricted with longitudinal relaxivity, r 1  = 4.37 mM −1  s −1 at 4.7 T. However, addition of Ca 2+ triggers a marked enhancement in r 1  = 6.99 mM −1  s −1 at 4.7 T (60% increase). The construct is highly selective for Ca 2+ over competitive metal ions at extracellular concentration. The r 1 is modulated by changes in the hydration number (0.2 to 1.05), which was confirmed by luminescence emission lifetimes of the analogous Eu 3+ complex. T 1 phantom images establish the capability of complex of visualizing changes in [Ca 2+ ] by MRI.