The release of Gd from all linear Gd3+ complexes in human serum was several orders of magnitude greater than predicted by the conditional stability constants. After 15 days, release of Gd3+ from the nonionic linear GBCAs was about 10 times higher than from the ionic linear GBCAs. Elevated serum phosphate levels accelerated the release of Gd3+ from nonionic linear GBCAs and, to a lesser degree, from the ionic linear GBCAs. All 3 macrocyclic GBCAs remained stable in human serum at both normal and elevated phosphate levels.
In 1988, the first contrast agent specifically designed for magnetic resonance imaging (MRI), gadopentetate dimeglumine (Magnevist®), became available for clinical use. Since then, a plethora of studies have investigated the potential of MRI contrast agents for diagnostic imaging across the body, including the central nervous system, heart and circulation, breast, lungs, the gastrointestinal, genitourinary, musculoskeletal and lymphatic systems, and even the skin. Today, after 25 years of contrast-enhanced (CE-) MRI in clinical practice, the utility of this diagnostic imaging modality has expanded beyond initial expectations to become an essential tool for disease diagnosis and management worldwide. CE-MRI continues to evolve, with new techniques, advanced technologies, and novel contrast agents bringing exciting opportunities for more sensitive, targeted imaging and improved patient management, along with associated clinical challenges. This review aims to provide an overview on the history of MRI and contrast media development, to highlight certain key advances in the clinical development of CE-MRI, to outline current technical trends and clinical challenges, and to suggest some important future perspectives.FundingBayer HealthCare.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0275-4) contains supplementary material, which is available to authorized users.
A preclinical experimental setting has been established where NSF-like lesions could be observed. The link between the application of Gd-based contrast media and the induction of NSF-like lesions was established. The data indicate that the observed skin lesions are related to the release of Gd and not to the depletion of endogenous ions. The investigations further suggest potential importance of the stability of Gd-based contrast agents.
Gd-Ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a highly water-soluble paramagnetic contrast agent. Due to its protein binding of about 10% and its lipophilic residue, Gd-EOB-DTPA exhibits both renal (30% of the dose) and hepatobiliary (70%) excretion in rats. Despite its lipophilic character, the compound displays a low toxicity (LD50 = 7.5 mmol/kg). T1-relaxivity of 5.3 liters mmol-1 s-1 in water, 8.7 liters mmol-1 s-1 in plasma, and 16.9 liters mmol-1 s-1 in rat liver together with the hepatocellular uptake explain the liver-specific contrast enhancement of Gd-EOB-DTPA. The diagnostic dose is considerably lower than the amount of Magnevist used in abdominal imaging. The preclinical studies suggest its clinical role as being a hepatobiliary contrast agent for MRI.
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