Iopamidol is one of the most common contrast media used for diagnostic CT-based clinical protocols. Chemically, this molecule contains two pools of mobile protons (amide and alcoholic) that are in exchange with water. At 7.05 T, pH 7.4, and 312 K, the exchange rate of the alcoholic protons is too fast to affect the NMR properties of water protons, whereas the slowly exchanging amide protons induce a T 2 -shortening effect on the "bulk" water signal that is detectable when the concentration is about 12 mM. Moreover, a more pronounced contrast is observed when the amide resonances are saturated by the application of an appropriate RF irradiation field, making iopamidol a potential chemical exchange saturation transfer (CEST) agent whose effect can be detected at a concentration as low as 7 mM (at 7.05 T). Iopamidol has been used as diagnostic agent for clinical CT protocols since 1981. This nonionic contrast medium for X-ray imaging has very broad diagnostic applications, including disorders of the central nervous system, the cardiovascular apparatus, and the urinary tract (1-5).The high water solubility shown by iopamidol, coupled with a very low toxicity, means that it can be safely administered intravenously at very high doses (up to 400 mg/ml).In addition to the three iodine atoms necessary for endowing the system with high X-ray radiopacity, the chemical structure of iopamidol (chart 1) is characterized by the presence of three amide functionalities bearing hydrophilic substituents that are responsible for its outstanding water solubility.Iopamidol possesses a high number of mobile protons (e.g., amide and alcoholic protons). We surmised that the occurrence of such a large pool of exchanging protons could be exploited as a source of contrast in an MR image. In fact, it is well established that proton exchange causes an increase in the water proton transverse relaxation rate (T 2 agent) (6 -8), and may produce a more pronounced image contrast if the exchanging proton pool is irradiated with the appropriate radiofrequency (RF). This should lead to a decrease in the signal intensity of the water protons through the so-called chemical exchange saturation transfer (CEST) process (9). Both mechanisms contribute to a reduction in the MR signal intensity of the water protons, thus resulting in a darker spot in the MR image.In this paper we report an in vitro study aimed at assessing the properties of iopamidol as a dual (T 2 and CEST) MRI contrast agent. In principle, if additional information can be gained from the MRI modality, one can envisage the potential clinical use of iopamidol in patients undergoing a CT exam. MATERIALS AND METHODS Iopamidol was kindly provided by Bracco Imaging, S.p.A (Milan, Italy). NMR MeasurementsAll of the MR images were obtained on a Bruker Avance 300 WB spectrometer equipped with a microimaging probe head (Micro 2.5). The measurements were carried out on a phantom made of seven capillaries (ϳ1 mm diameter) contained inside a 10-mm NMR tube filled with neat water. A 10-mm RF insert ( 1...

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BOPTA, (9R,S)-2,5,8-Tris(carboxymethyl)-12-phenyl-11-oxa-2,5,8-triazadodecane-1,9-dicarboxylic acid, is a chelating agent whose gadolinium complex can be used as a magnetic resonance imaging contrast agent (MRI-CA) specific for the liver. The stepwise deprotonation constants for BOPTA were determined from a series of 13 C NMR measurements by means of the new computer program HYPNMR and also from potentiometric titration data by means of the program HYPERQUAD. The first three stepwise protonation constants obtained by the NMR method are in very good agreement with those determined by potentiometry. In very acidic solutions the NMR method gave more reliable results because the glass electrode is susceptible to interference at low pH.The enthalpy changes for the protonation reactions have also been measured by microcalorimetry. The first two protonation reactions are exothermic, indicating that protonation occurs on amine nitrogen atoms, while the following protonation steps, being athermic, involve carboxylate groups.

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