A manganese(II)-Based Responsive Contrast Agent Detects Glucose- Stimulated Zinc Secretion from the Mouse Pancreas and Prostate by MRI.

A Mn(II)-based zinc-sensitive MRI contrast agent, Mn(PyC3A)-BPEN, was prepared and characterized and the agent was used in imaging experiments to detect glucose-stimulated zinc secretion (GSZS) from the mouse pancreas and prostate in vivo. Thermodynamic and kinetic stability tests showed that Mn(PyC3A-BPEN) has superior kinetic inertness compared to Gd(DTPA), is less susceptible to transmetallation in the presence of excess Zn2+ ions, and less susceptible to transchelation by albumin. In comparison with other gadolinium-based zinc sensors bearing a single zinc binding moiety, Mn(PyC3A-BPEN) appears to be a reliable alternative for imaging b-cell function in the pancreas and glucose-stimulated zinc secretion from prostate cells

A Responsive MRI Contrast Agent for Detection of Excess copper(II) in the Liver in Vivo

The design, synthesis, and properties of a new gadolinium-based copper-responsive MRI contrast agents are presented in detail here. The sensor (GdL1) has high selectivity for copper ions and exhibits a 47% increase in r1 relaxivity upon binding to 1 equivalent of Cu2+ in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r1 relaxivity is amplified even further up to 270%. Additional spectroscopic and XAS studies show that Cu2+ is coordinated by two carboxylic acid groups and the single amine group on an appended side-chain of GdL1 and forms a ternary complex with HSA (GdL1-Cu2+-HSA). T1-weighted in vivo imaging demonstrates that GdL1 can detect basal, endogenous labile copper(II) ions in living mice. This offers a unique opportunity to explore the role of copper ions in the development and progression of neurological diseases such as Wilson disease. </div

Enhancing <i>r</i>₁ Relaxivity in GdDOTA-Monoamide Complexes through Polar Group-Mediated Ordering of Second-Sphere Water Molecules

This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in r1 relaxivity from 3.0 to 6.3 mM–1 s–1 at 20 MHz as the pH was lowered from 9 to 2.5. In comparison to the bis-, tris-, and tetrakis-phosphonate analogues, which all show a biphasic dependence of r1 with changes in pH, the unique r1 versus pH characteristics of GdDOTA-1AmP are shown to closely parallel deprotonation of the single appended phosphonate group. Although the tissue biodistribution and clearance rates of GdDOTA-1AmP are more favorable than the other more highly charged phosphonate derivatives, the pH dependency of r1 is substantially reduced at magnetic fields typically used for small animal imaging (7 and 9.4T), so the attractiveness of this new molecule for quantitative imaging of tissue pH is diminished. However, this study provides some new insights into the feasibility of designing pH-responsive MRI contrast agents based upon fundamental acid–base prototropic mechanisms