Gadobutrol gradually reduces cell density under neutron irradiation as concentration increases [1].

In female C57BL/6 N mice, intrathecal injection of 200 mM dobutril administered once a week can markedly improve intracerebroventricular cell signaling [2].

Cell viability assay [1]
Cell Types: Human melanoma cell line Sk-Mel-28
Tested Concentrations: 0-30 mM
Incubation Duration: 1 hour
Experimental Results: Cell density diminished to 26% at 30 mM, compared with cells without gadobutrol Density drops to 80% under neutron irradiation.

Animal/Disease Models: Female C57BL/6 N mice, 11-13 weeks, 21-23 g)[2]
Doses: 200 mM
Route of Administration: intravenous (iv) (iv)injection; once; one week
Experimental Results: cells in habenula, hippocampal formation and locus coeruleus Signal boost.

Absorption, Distribution and Excretion
After intravenous administration, gadobutrol is rapidly distributed in the extracellular space. After a gadobutrol dose of 0.1 mmol/kg body weight, an average level of 0.59 mmol gadobutrol/L was measured in plasma 2 minutes after the injection and 0.3 mmol gadobutrol/L 60 minutes after the injection. Gadobutrol does not display any particular protein binding. Following GBCA administration, gadolinium is present for months or years in the brain, bone, skin, and other organs. The mean AUC of gadobutrol in patients with normal renal function was 1.1 ± 0.1 mmol∙h/L, compared to 4.0 ± 1.8 mmol∙h/L in patients with mild to moderate renal impairment and 11.5 ± 4.3 mmol∙h/L in patients with severe renal impairment.
Gadobutrol is excreted in an unchanged form via the kidneys. Within two hours after intravenous administration more than 50% and within 12 hours more than 90% of the given dose is eliminated via the urine. Extra-renal elimination is negligible.
In children aged 2 to 17, the body weight-normalized median total volumes of distribution (L/kg) were estimated to be 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6-year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group.
In healthy subjects, renal clearance is 1.1 - 1.7mL/(min·kg). Clearance was observed to be slightly lower in elderly subjects, when using a 0.1 mmol/kg dose.
After intravenous administration, gadobutrol is rapidly distributed in the extracellular space. After a gadobutrol dose of 0.1 mmol/kg body weight, an average level of 0.59 mmol gadobutrol/L was measured in plasma 2 minutes after the injection and 0.3 mmol gadobutrol/L 60 minutes after the injection. Gadobutrol does not display any particular protein binding. In rats, gadobutrol does not penetrate the intact blood-brain barrier.
In rat lactation studies, gadobutrol was present in milk in amounts less than 0.1% of the dose intravenously administered and the gastrointestinal absorption is poor (approximately 5% of the dose orally administered was excreted in the urine). In lactating rats receiving 0.5 mmol/kg of intravenous [153Gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the pup via maternal milk, within 3 hours after administration.

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Metabolism / Metabolites
Gadobutrol is not metabolized.

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Biological Half-Life
For adult patients, the half-life was estimated to be 1.80 (1.20, 6.55) hours. For pediatric aged 0 to <2 years, 2 to 6 years, 7 to 11 years, and 12 to < 18 years, the half-life was calculated to be 2.91 (1.60, 12.4), 1.91 (1.04, 2.70), 1.66 (0.91, 2.71), and 1.68 (1.31, 2.48) hours respectively.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Gadobutrol is one of the most stable gadolinium agents, theoretically making it one of the safer drugs to use during breastfeeding. Guidelines developed by several professional organizations state that breastfeeding need not be disrupted after a nursing mother receives a gadolinium-containing contrast medium. However, because there is no published experience with gadobutrol during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
No information is available on the protein binding of gadobutrol.

[1]. Gadolinium neutron capture therapy (GdNCT) of melanoma cells and solid tumors with the magnetic resonance imaging contrast agent Gadobutrol. Invest Radiol. 1999 Feb;34(2):126-33.

[2]. Gadobutrol enhances T1-weighted MRI of nerve cells. Toxicol Lett. 2019 Jun 15;308:17-23.

[3]. Cheng KT. Gadobutrol. Molecular Imaging and Contrast Agent Database (MICAD).

Gadobutrol is a second-generation extracellular non-ionic macrocyclic GBCA (gadolinium-based contrast agent) used in magnetic resonance imaging (MRI) in adults and children older than 2 years of age. Due to its physicochemical properties, gadobutrol is formulated at twice the gadolinium ion concentration compared to other GBCA and thus requires a lesser injection volume. Like other GBCA, gadobutrol usage carries the risk of nephrogenic systemic fibrosis (NSF) due to the dissociation of gadolinium from the chelates, although gadobutrol tends to have a lower risk of NSF thanks to the macrocyclic structures that limit dechelation of gadolinium.
Gadobutrol is a Gadolinium-based Contrast Agent. The mechanism of action of gadobutrol is as a Magnetic Resonance Contrast Activity.
Gadobutrol is a gadolinium-based, hydrophilic, macrocyclic, electrically neutral contrast agent used in contrast-enhanced MRI (CE-MRI). Gadobutrol is a non-ionic, paramagnetic complex consisting of gadolinium (Gd3+) chelated with the macrocyclic compound dihydroxy-hydroxymethylpropyl-tetraazacyclododecane-triacetic acid (butrol). Following intravenous administration, gadobutrol may increase MRI sensitivity for the detection of tumors and inflammatory and demyelinating diseases of the central nervous system (CNS) that are associated with areas with blood-brain barrier defects due to altered perfusion or an enlarged extracellular space. This agent is eliminated in an unchanged form via the kidneys; extra-renal elimination is negligible.
See also: Gadolinium Cation (3+) (has active moiety).

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Drug Indication
Gadobutrol is indicated for use with magnetic resonance imaging for the following diagnostic processes: - To detect and visualize areas with disrupted blood-brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients, including term neonates. - To assess the presence and extent of malignant breast disease in adult patients - To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients, including term neonates - To assess myocardial perfusion (under stress and at rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease
FDA Label
Diagnostic evaluation of tissue pathologies with contrast-enhanced magnetic resonance imaging (MRI)

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Mechanism of Action
In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occur with differences in proton density, the spin-lattice or longitudinal relaxation times (T1), and the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadobutrol shortens the T1 and T2 relaxation times. The extent of decrease of T1 and T2 relaxation times, and therefore the amount of signal enhancement obtained from gadobutrol, is based upon several factors including the concentration of gadobutrol in the tissue, the field strength of the MRI system, and the relative ratio of the longitudinal and transverse relaxation times. At the recommended dose, the T1 shortening effect is observed with the greatest sensitivity in T1-weighted magnetic resonance sequences. In T2*-weighted sequences, the induction of local magnetic field inhomogeneities by the large magnetic moment of gadolinium and at high concentrations (during bolus injection) leads to a signal decrease.

C18H31N4O9GD

604.71

605.133

770691-21-9

Gadobutrol hydrate;198637-52-4

6102852

White to off-white solid powder

3

13

7

32

532

2

C1CN(CCN(CCN(CCN1CC(=O)[O-])CC(=O)[O-])[C@H](CO)[C@@H](CO)O)CC(=O)[O-].[Gd+3]

ZPDFIIGFYAHNSK-CTHHTMFSSA-K

InChI=1S/C18H34N4O9.Gd/c23-12-14(15(25)13-24)22-7-5-20(10-17(28)29)3-1-19(9-16(26)27)2-4-21(6-8-22)11-18(30)31;/h14-15,23-25H,1-13H2,(H,26,27)(H,28,29)(H,30,31);/q;+3/p-3/t14-,15-;/m1./s1

2-[4,10-bis(carboxylatomethyl)-7-[(2R,3S)-1,3,4-trihydroxybutan-2-yl]-1,4,7,10-tetrazacyclododec-1-yl]acetate;gadolinium(3+)

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~20 mg/mL (~33.07 mM)

Solubility in Formulation 1: 50 mg/mL (82.68 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)