![]() ![]() Gd-HP-D03A and Gd-DTPA-MBA are non-ionic (uncharged or with a zero net charge). Gd-DTPA and Gd-DOTA are ionic (charged), with -2 and -1 charge in solution, respectively. These differences lead to the greater formulation and dosing flexibility for the uncharged or neutral charged chelates and reduced Gd-chelate dissociation for those built around a macrocyclic ligand framework (Ibrahim MA, Ph.D. Differences in physicochemical properties are structural design features, i.e., the presence or absence of overall negative charge on the Gd-chelate complex, use of linear or macrocyclic frameworks for the organic chelating ligands. These agents are broadly similar - highly water-soluble gadolinium chelates that extracellularly distributed and eliminated rapidly through renal glomerular filtration. Although numerous studies published in peer-reviewed journals have confirmed the safety and efficacy of the seven gadolinium-based, MRI contrast agents approved for CNS imaging, differences among these agents and the impact these differences may have on clinical decision-making and diagnostic sensitivity remain misunderstood and sometimes underappreciated. Ablavar is an intravascular “blood-pool” agent approved for MR angiography of the aorto-iliac vessels, whose strong binding to serum albumin (and large effective molecular size) restricts permeability across the open blood-brain barrier, which limits CNS suitability applications, while Eovist is an approved liver-specific agent inappropriate for CNS applications because 50% of the injected dose is taken up and eliminated by hepatocytes. ![]() Two other agents that are not approved for Contrast-Enhanced MR imaging of the CNS (gadofosveset trisodium and gadoxetic acid have distinct properties that render them unsuitable for this indication. Six more MRI contrast agents were approved by FDA for clinical use from 1995 through 2017: gadopentetate dimeglumine (gadolinium diethylene triamine pentaacetic acid (Gd-DTPA), gadodiamide (gadolinium diethylene triamine penta-acetic acid bis-methylamide (GD-DTPA-BMA), Gadoteridol (Gadolinium-1,4,7- tris (carboxymethyl)-10-(2' hydroxypropyl)-1, 4, 7 -10-tetraazacyclododecane (Gd-HPD03A]), gadoterate meglumine (gadolinium-tetraazacyclododecane tetra acetic acid (Gd-DOTA), Dotarem®, gadobenate dimeglumine gadobutrol. Three MRI contrast agents have been approved for clinical use in the United States as of 1994. All four contrast agents approved for clinical use alter the relaxation times of tissues. Each is a tissue characteristic that influences MRI signal intensity and, in theory, a parameter that can be manipulated pharmacologically for the purpose of contrast enhancement. The determinants of signal intensity and contrast in MRI are spin density (p), susceptibility (x), proton relaxation (T and T), and motion (diffusion and perfusion). Further, MRI is neither quantitatively nor parametrically singular in its contrast mechanism, as is computed tomography. All other diagnostic imaging modalities depend on one inherent tissue property for image formation. MRI is unique among diagnostic modalities because it uses more than one intrinsic property of the tissue being imaged. Strategic localization of the agent can regionally change the tissue properties and result in preferential enhancement. They serve to improve the sensitivity and specificity of diagnostic images by altering the intrinsic properties of tissues, which influence the fundamental mechanisms of contrast. Contrast agents are pharmaceuticals that increase the information content of diagnostic images. ![]()
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