Preclinical Safety Assessment and Pharmacokinetics of Gadodiamide Injection, a New Magnetic Resonance Imaging Contrast Agent

Harpur, Ernest S.; Worah, Dilip; Hals, Petter‐Arnt; Holtz, E.; Furuhama, Kazuhisa; Nomura, Hisashi

doi:10.1097/00004424-199303001-00004

Cited by 149 publications

(100 citation statements)

References 6 publications

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“…Both CAs are primarily eliminated by the kidneys from the blood stream, as indicated by the high Gd accumulation in the kidney medulla. The data obtained here are in accordance with previous reports on the pharmacokinetics of GdDOTA (11) or other small molecular weight Gd-based contrast agents (12).…”

Section: Dce-mri In Vivosupporting

confidence: 92%

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Livramento

Weidensteiner

Prata

et al. 2006

Contrast Media Mol Imaging

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À ¼ GdDOTA). The metallostar was well tolerated by the animals at the concentrations of 0.0500 (high dose) and 0.0125 (low dose) mmol Gd kg À1 body weight; (BW). The signal enhancement in the inversion recovery fast low angle shot (IR FLASH) images after the high-dose metallostar injection was considerably higher than after GdDOTA injection (0.1 mmol Gd kg À1 BW), despite the higher dose of the latter. The high-dose metallostar injection resulted in a greater drop in the spin-lattice relaxation time (T 1 ), as calculated from the inversion recovery true fast imaging with steady-state precession (IR TrueFISP) data for various tissues, than the GdDOTA or the low dose metallostar injection. In summary, these studies have confirmed that the approximately four times higher relaxivity measured in vitro for the metallostar is retained under in vivo conditions. The pharmacokinetics of the metallostar was found to be similar to that of GdDOTA, involving fast renal clearance, a leakage to the extracellular space in the muscle tissue and no leakage to the brain. As expected on the basis of its moderate molecular weight, the metallostar does not function as a blood pool agent. The dynamic g scintigraphic studies performed in Wistar rats with the metallostar compound having 153 Sm enrichment also proved the renal elimination pathway. The biodistribution experiments are in full accordance with the MR and scintigraphic imaging. At 15 min post-injection the activity is primarily localized in the urine, while at 24 h post-injection almost all radioactivity is cleared from tissues and organs.

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Section: Dce-mri In Vivosupporting

confidence: 92%

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Livramento

Weidensteiner

Prata

et al. 2006

Contrast Media Mol Imaging

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“…As aforementioned, previous researchers attributed skin lesions seen in rats after the repeated administration of high-dose nonionic linear GBCAs to a depletion of Zn ions due to the presence of excess ligand in the commercial formulations of these agents (41,42). Indeed, increased urinary excretion of Zn after the administration of linear GBCAs has been described in several experiments with species including humans (12,33,36).…”

Section: Role Of Zincmentioning

confidence: 88%

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

Magnetic Resonance Imaging

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Nephrogenic systemic fibrosis (NSF) is a potentially severe systemic disease typically characterized by fibrosis of the skin and connective tissues. The etiology of NSF is still unknown but is likely to be multifactorial. Specific triggers under scientific evaluation have included surgery and/or the occurrence of thrombosis or other vascular injury, proinflammatory state, the administration of high doses of erythropoietin, and more recently the use of gadolinium-based contrast agents (GBCAs). The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on animal experiments. The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.

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“…7a). To compensate for their lower stability, the non-ionic linear compounds, Omniscan and OptiMark, are formulated with 5 mol% and 10 mol% excess ligand, respectively [23].…”

Section: Discussionmentioning

confidence: 99%

Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions

et al. 2008

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Preclinical Safety Assessment and Pharmacokinetics of Gadodiamide Injection, a New Magnetic Resonance Imaging Contrast Agent

Cited by 149 publications

References 6 publications

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions

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