Here we report on a dual‐modal ¹⁹F and ¹H MRI paramagnetic probe with a self‐immolative linker, Gd–DOMF–Gal. The enzymatic conversion of this probe by β‐galactosidase resulted in a simultaneous turning on of the fluorine signal and changed ability of the Gd³⁺ complex to modulate the ¹H MR signal intensity of the surrounding water molecules. A versatile imaging platform for monitoring a variety of enzymes by ¹⁹F and ¹H MRI using this molecular design is proposed. Copyright © 2012 John Wiley & Sons, Ltd.

A molecule bearing a macrocyclic DOTA-type chelator and an acyclic chelator based on the 5-aminoisophthalamide diethylenediaminetetraacid (5A-PADDTA) was synthesized by linking these two moieties via an amide bond. The ligand has the possibility to complex two identical or different lanthanide ions, depending on the desire for its potential application. Luminescence studies involving titrations of the Eu³⁺ or Gd³⁺ complex with Tb³⁺ confirm the formation of heterometallic complexes, as well as the presence of different species in the solution. Comparative ¹H NMR spectra of the ligand, its Eu³⁺ complex, and that containing both Eu³⁺ and Tb³⁺ proves the existence of respective monometallic or bimetallic species. NMR diffusion measurements on 5A-PADDTA as a model compound indicate the formation of aggregates upon the addition of Y³⁺ (chosen as a diamagnetic analogue of lanthanide ions). Hydration values were calculated from the respective luminescence lifetime values. They show the dominance of a q = 1 species for both ions in monometallic complexes, or q = 1 and q = 2 species of ions in aggregated complexes, for DOTA and 5A-PADDTA chelators, respectively.

Calcium‐sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI‐based method capable of determining diffusion properties of conventional and calcium‐sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium‐sensitive contrast agents. The full pharmacokinetic time‐course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel‐wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look–Locker‐based quantitative T₁ mapping, and T₁‐weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2–4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium‐sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration. Copyright © 2014 John Wiley & Sons, Ltd.

A new series of Gd³⁺ complexes based on DO3A (GdL¹–GdL⁴) was synthesized and investigated. They possess side chains with different structures which determine their varying binding properties and response towards endogenous metal ions, measured by changes in the longitudinal relaxivity (r₁). GdL⁴ exhibits the highest selectivity toward Ca²⁺ in comparison to the other complexes, with up to a 63% increase of the r₁. GdL² and GdL³ also respond to different Ca²⁺ concentration ranges, however with a lower selectivity since the r₁ changes are also observed in the presence of other cations such as Mg²⁺, Zn²⁺ or Cu²⁺. Assessment of the hydration number (q) via luminescence lifetime measurements confirmed that the change in q is responsible for the r₁ response for all the complexes.