Iopamidol: Exploring the potential use of a well‐established x‐ray contrast agent for MRI

Abstract

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...

Encoding the frequency dependence in MRI contrast media: the emerging class of CEST agents

“…Later, our group explored the CEST properties of iopamidol, a small diamagnetic molecule widely used as contrast agent in CT clinical protocols (24). Besides the three iodine atoms necessary for the X-ray detection, iopamidol contains three pseudo-equivalent exchanging amide protons (Dv offset 4.1 ppm).…”

Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI

“…Our specific “acidoCEST MRI” protocol measures the two CEST signals produced by the amide protons of iopamidol (Isovue ™ , Bracco Imaging, Inc.), which is FDA-approved for clinical CT studies that we have repurposed for CEST MRI exams [10]. These CEST signals are linearly correlated with pH because the exchange of amide protons and water protons is base-catalyzed [11].…”

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents

“…5 Recently, it has been shown that iopamidol is suitable for producing MRI contrast by exploiting the chemical exchange saturation transfer (CEST) approach based on the transfer of saturated magnetization to the water resonance via chemical exchange, causing a decrease in the water signal intensity. 6 As originally demonstrated by Ward et al, 7 CEST-MRI is a unique contrast mechanism that is sensitive to contrast media concentration and local properties such as pH and temperature. [8][9][10][11][12][13] Notably, iodinated agents such as iopamidol and iopromide, containing 2 nonequivalent groups of amide protons, allow the setup of a ratiometric procedure for in vivo pH mapping in different tissues and pathological models.…”