Contrast-to-Dose Relationship of Gadopiclenol, an MRI Macrocyclic Gadolinium-based Contrast Agent, Compared with Gadoterate, Gadobenate, and Gadobutrol in a Rat Brain Tumor Model.

Abstract

Background Detection of cerebral lesions at MRI may benefit from a chemically stable and more sensitively detected gadolinium-based contrast agent (GBCA). Gadopiclenol, a macrocyclic GBCA with at least twofold higher relaxivity, is currently undergoing clinical trials in humans. Purpose To determine the relationship between MRI contrast enhancement and the injected dose of gadopiclenol in a glioma rat model compared with those of conventional GBCA at label dose. Materials and Methods Between April and July 2012, 32 rats implanted with C6 glioma received two intravenous injections at a 24-hour interval. The injections were randomly selected among five doses of gadopiclenol (0.025, 0.05, 0.075, 0.1, and 0.2 mmol/kg) and three reference GBCAs (gadoterate meglumine, gadobutrol, and gadobenate dimeglumine) at 0.1 mmol/kg. MRI tumor enhancement was assessed on T1-weighted images before and up to 30 minutes after injection. Two blinded radiologists visually and qualitatively scored contrast enhancement, border delineation, and visualization of tumor morphology. Quantitatively, variations in contrast-to-noise ratio (ΔCNR) between tumor and contralateral parenchyma were calculated at each time point and were compared for each treatment at 5 minutes by using a mixed model after normality test. Results A total of 24 rats underwent the complete protocol (n = 5-7 per group). A linear dose-dependent ΔCNR relationship was observed between 0.025 and 0.1 mmol/kg for gadopiclenol (R 2 = 0.99). No difference in ΔCNR was observed between the three reference GBCAs (P ≥ .55). Gadopiclenol resulted in twofold higher ΔCNR at 0.1 mmol/kg (P < .001 vs gadobutrol and gadoterate, P = .002 vs gadobenate) and similar ΔCNR at 0.05 mmol/kg (P = .56, P > .99, and P = .44 compared with gadobutrol, gadobenate, and gadoterate, respectively). For both readers, 0.05 mmol/kg of gadopiclenol improved contrast enhancement, border delineation, and visualization of tumor morphology (scores > 3 compared with scores between 2 and 3 for the marketed GBCA). Conclusion Gadopiclenol at 0.05 mmol/kg yielded comparable change in contrast-to-noise ratio and morphologic characterization of brain tumors compared with gadobenate, gadoterate, or gadobutrol at 0.1 mmol/kg. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Tweedle in this issue.

• Authors: Philippe Robert, Véronique Vives, Anne-Laure Grindel, Stéphane Kremer, Guillaume Bierry, Gaelle Louin, Sébastien Ballet, Claire Corot
• Journal: Radiology (Radiology) Vol. 294 Issue 1 Pg. 117-126 (01 2020) ISSN: 1527-1315 [Electronic] United States
• PMID: 31660804 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Azabicyclo Compounds
• Contrast Media
• Heterocyclic Compounds
• Organometallic Compounds
• gadobenic acid
• gadobutrol
• Meglumine
• gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
• Gadolinium
• gadopiclenol

Topics

• Animals
• Azabicyclo Compounds (administration & dosage)
• Brain (diagnostic imaging)
• Brain Neoplasms (diagnostic imaging)
• Contrast Media (administration & dosage)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Gadolinium (administration & dosage)
• Glioma (diagnostic imaging)
• Heterocyclic Compounds (administration & dosage)
• Image Enhancement (methods)
• Magnetic Resonance Imaging (methods)
• Meglumine (administration & dosage, analogs & derivatives)
• Organometallic Compounds (administration & dosage)
• Rats
• Sensitivity and Specificity