It has been demonstrated that divalent zinc ions packaged with insulin in β-cell granules can be detected by MRI during glucose-stimulated insulin secretion using a gadolinium-based Zn 2+sensitive agent. This study was designed to evaluate whether a simpler agent design having single Zn 2+-sensing moieties but with variable Zn 2+ binding affinities might also detect insulin secretion from the pancreas. Using an implanted MR-compatible window designed to hold the pancreas in a fixed position for imaging, we now demonstrate that focally intense "hot spots" can be detected in the tail of the pancreas using these agents after administration of glucose to stimulate insulin secretion. Histological staining of the same tissue verified that the hot spots identified by imaging correspond to clusters of islets, perhaps reflecting first-responder islets that are most responsive to a sudden increase in glucose. A comparison of images obtained when using a high-affinity Zn 2+ sensor versus a lower-affinity sensor showed that the lower-affinity sensors produced the best image contrast. An equilibrium model that considers all possible complexes formed between Zn 2+ , the GdL sensor, and HSA predicts that a GdL sensor with lower affinity for Zn 2+ generates a lower background signal from endogenous Zn 2+ prior to glucose-stimulated insulin secretion (GSIS) and that the weaker binding affinity agent is more responsive to a further increase in Zn 2+ concentration near β-cells after GSIS. These model predictions are consistent with the in vivo imaging observations.

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 Cu 2+ 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 Cu 2+ 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-Cu 2+-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.

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 Zn 2+ 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 -cell function in the pancreas and glucose-stimulated zinc secretion from prostate cells.

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 <i>in vivo</i>. 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.

<div> <p>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 <i>in vivo</i> 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.</p> </div>