Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent

Abstract

Calcium [Ca(II)] is a fundamental transducer of electrical activity in the central nervous system (CNS). Influx of Ca(II) into the cytosol is responsible for action potential initiation and propagation, and initiates interneuronal communication via release of neurotransmitters and activation of gene expression. Despite the importance of Ca(II) in physiology, it remains a challenge to visualize Ca(II) flux in the central nervous system (CNS) in vivo. To address these challenges, we have developed a new generation, Ca(II)-activated MRI contrast agent that utilizes ethyl esters to increase cell labeling and prevent extracellular divalent Ca(II) binding. Following labeling, the ethyl esters can be cleaved, thus allowing the agent to bind Ca(II), increasing relaxivity and resulting in enhanced positive MR image contrast. The ability of this probe to discriminate between extra- and intracellular Ca(II) may allow for spatiotemporal in vivo imaging of Ca(II) flux during seizures or ischemia where large Ca(II) fluxes (1–10 μM) can result in cell death.

Intracellular Transport Studies of Picolinate Macrocyclic Copper and Lanthanide Complexes

“…Structural modifications of metallic complexes influence cell uptake, and allow their utilization as probes for intracellular targets . For instance, some of these complexes can stain the lysosomes selectively, or can detect intracellular Ca 2+ . Previously, it was shown that several Tb and Eu complexes are capable of entering cells via macropinocytosis .…”

Gd-Complex of a Rosmarinic Acid Conjugate as an Anti-Inflammatory Theranostic Agent via Reactive Oxygen Species Scavenging

“…Lipophilicity measurements were performed using a previously described method [ 18 ]. GdL (3) was dissolved in water to a volume of 1 mL at a concentration of 1 mM and mixed with the same volume of 1-octanol.…”

Activatable probes for diagnosis and biomarker detection by MRI

“…35,36 Kim et al 34 (Figure 4). [43][44][45] Probes based on this mechanism have been used to monitor intracellular Ca (II) in hippocampal neuronal cells 43 and astrocytes. 44 The same OFF/ON strategy was used but using a Gd chelate modified for Ca (II) complexation linked to a dendrimer.…”