Gadobutrol

Gadobutrol (CAS No. 770691-21-9; 138071-82-6) is a macrocyclic gadolinium-based MRI contrast agent (GBCA). Its core function is to shorten the T1 relaxation time of water molecules in vivo to enhance MRI signal, and it does not produce inhibitory, activating, or antagonistic target effects; it is involved in the MRI T1-weighted imaging relaxation enhancement pathway and the renal excretion pathway of the parent compound. Due to its high kinetic stability, it does not participate in in vivo transmetalation or neurotoxicity-related apoptotic pathways.

In animal models, it is used for model intervention in mouse experimental autoimmune encephalomyelitis (EAE, a multiple sclerosis model), for in vivo gadolinium retention and pharmacokinetic studies in rats, and for safety evaluation in humanized MRGPRX2 mast cell mice.

In terms of application concentrations, cell culture (rat organotypic hippocampal slices) commonly uses 1, 10, and 50 mM, with no cytotoxicity; in animal experiments, mice in the EAE model receive tail vein injections of 2.5 mmol/kg/time (cumulative 20 mmol/kg), and rats receive a single intravenous injection of 0.6 mmol Gd/kg; clinically, as a diagnostic contrast agent, the standard dose is 0.1 mmol/kg, and it is rapidly cleared by the kidneys as an intact chelate. Under neuroinflammatory conditions, brain gadolinium retention can decrease to below 0.38±0.08 μM by 40 days after dosing, with no neurotoxicity or mast cell activation-related allergic reactions.

References:

[1] Mencarelli A, Gunawan M, Yong KSM, Bist P, Tan WWS, Tan SY, Liu M, Huang EK, Fan Y, Chan JKY, Choi HW, Abraham SN, Chen Q. A humanized mouse model to study mast cells mediated cutaneous adverse drug reactions. J Leukoc Biol. 2020 May;107(5):797-807. doi: 10.1002/JLB.3MA1219-210RR. Epub 2020 Jan 10. PMID: 31922289; PMCID: PMC7322799.

[2] Anderhalten L, Silva RV, Morr A, Wang S, Smorodchenko A, Saatz J, Traub H, Mueller S, Boehm-Sturm P, Rodriguez-Sillke Y, Kunkel D, Hahndorf J, Paul F, Taupitz M, Sack I, Infante-Duarte C. Different Impact of Gadopentetate and Gadobutrol on Inflammation-Promoted Retention and Toxicity of Gadolinium Within the Mouse Brain. Invest Radiol. 2022 Oct 1;57(10):677-688. doi: 10.1097/RLI.0000000000000884. Epub 2022 Apr 21. PMID: 35467573; PMCID: PMC9444290.

[3] Parakkattel D, Ruprecht N, Broekmann P, Guimbal S, Stüdle C, Soldati S, Heverhagen JT, Engelhardt B, von Tengg-Kobligk H. Identifying a potential role of immune cells in gadolinium deposition within the brain. Fluids Barriers CNS. 2025 Jul 29;22(1):80. doi: 10.1186/s12987-025-00674-5. PMID: 40731338; PMCID: PMC12306026.

[4] Gruendemann S, Frenzel T, Lohrke J, Boyken J, Jost G, Berger M, Ulbrich HF, Pietsch H. In Vitro and In Vivo Stability Assessment of the Novel, Macrocyclic Gadolinium-Based Contrast Agent Gadoquatrane. Invest Radiol. 2025 Nov 1;60(11):768-778. doi: 10.1097/RLI.0000000000001195. PMID: 40359923; PMCID: PMC12490335.

[5] Bilgin B, Hekim MG, Adam M, Bulut F, Orhan SU, Tekin S, Husunet MT, Ozcan M. Pre-clinical safety assessments of gadobutrol in diabetes-induced neuropathy: In vivo, in vitro and in silico studies. Toxicol Lett. 2025 Nov;413:111733. doi: 10.1016/j.toxlet.2025.111733. Epub 2025 Sep 27. PMID: 41022339.