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

•DO3A-AME-NPHE for MRI has been developed based on DO3A and Phe framework.•It shows 60% change in relaxivity (T1) for Ca2+ (4.37 s−1 mM−1 vs 6.99 s−1 mM−1).•Highly selective for Ca2+ over metal ions of s and d block at extracellular concentration.•The q value changes from 0.2 to 1.05 in the presence of Ca2+.

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 Gd3+-DO3A core coupled to iminoacetate coordinating groups for calcium induced relaxivity switching. In the absence of Ca2+ ions, inner sphere water binding to the Gd-DO3A-AME-NPHE is restricted with longitudinal relaxivity, r1 = 4.37 mM−1 s−1 at 4.7 T. However, addition of Ca2+ triggers a marked enhancement in r1 = 6.99 mM−1 s−1 at 4.7 T (60% increase). The construct is highly selective for Ca2+ over competitive metal ions at extracellular concentration. The r1 is modulated by changes in the hydration number (0.2 to 1.05), which was confirmed by luminescence emission lifetimes of the analogous Eu3+ complex. T1 phantom images establish the capability of complex of visualizing changes in [Ca2+] by MRI.

Graphical abstractGd-DO3A-AME-NPHE was developed which exhibits a distinct Ca2+ triggered enhancement (ca 60%) in MR relaxivity with specific selectivity towards Ca2+ over s and d-block metal cations as shown in T1 phantom images.Figure optionsDownload full-size imageDownload as PowerPoint slide