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...
TS can recognize inhibitors that are dissimilar to, but that bind competitively with, the folate substrate. Combining structure-based discovery with in-parallel synthetic techniques allowed the rapid elaboration of this series of compounds. More automated versions of this approach can be envisaged.
Analysis of organic acids in strawberry-tree (Arbutus unedo) honey showed the presence of an unknown acid as the main constituent. This compound was isolated and identified as homogentisic acid (2, 5-dihydroxyphenylacetic acid) by MS and NMR techniques. Its average content in honey was 378 +/- 92 mg/kg. Analysis of nectar confirmed the floral origin of the compound found in honey. Since this acid was not detected in any of the different monofloral honeys, it could be used as a marker of strawberry-tree (A. unedo) honey.
Analytical measurements and proton nuclear magnetic resonance (1H NMR) spectra of phenolic extracts were performed on a set of italian extra‐virgin olive oils from different cultivars and geographical locations of Apulia region. Multivariate statistical analysis (principal component analysis, hierarchical clustering analysis, and discriminant analysis) was applied separately to analytical and NMR data. Analytical parameters, in particular fatty acid compositions, permit the discrimination of olive variety, while 1H NMR data of phenolic extracts permit a classification according to the geographical origin of the samples.
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