Original article
Diagnostic efficacy and safety of gadoteridol compared to gadobutrol and gadoteric acid in a large sample of CNS MRI studies at 1.5 T

https://doi.org/10.1016/j.neurad.2020.06.005Get rights and content

Highlights

  • Contrast-enhanced MRI plays a central role in diagnosis of neurological diseases.

  • Previous crossover studies didn’t evaluate contrast agents in clinical practice.

  • Gadoteridol is safe with good image quality in a wide-range of CNS-pathologies.

Abstract

Purpose

To evaluate safety and diagnostic accuracy of gadoteridol vs. other macrocyclic gadolinium-based contrast agents (GBCAs) in a large cohort of consecutive and non-selected patients referred for CE-MRI of the CNS.

Material and methods

Between November 2017 and March 2018, we prospectively enrolled a consecutive cohort of patients referred for neuroradiological CE-MRI (1.5 T MRI). Image quality and adverse events were assessed. Diagnostic performance was determined for a subgroup of patients with truth standard findings available. Comparison was made between patients receiving gadoteridol and patients receiving other macrocyclic GBCAs. Inter-reader agreement (kappa) between two expert neuroradiologists was calculated for the diagnosis of malignancy.

Results

Overall, 460 patients (220 M/240F; mean age 54 ± 16 years) were enrolled of which 230 received gadoteridol (Group 1) and 230 either gadoteric acid or gadobutrol [n = 83 (36.1%) and n = 147 (63.9%), respectively; Group 2]. Image quality was rated as good or excellent in both groups. The sensitivity, specificity and diagnostic accuracy for determination of malignancy was 88.2%, 96.5% and 95.4%, respectively, for Group 1 and 93.7%, 97.4% and 96.9%, respectively, for Group 2, with no significant differences between groups (P > 0.75) for any determination. Inter-reader agreement for the identification of malignancy was excellent [K = 0.877 (95%CI: 0.758–0.995) and K = 0.818 (95%CI: 0.663–0.972) for groups 1 and 2, respectively; P = 0.0913]. Adverse events occurred in 5 of 460 (1.09%) patients overall, with no significant difference (P = 0.972) between groups.

Conclusion

Gadoteridol was safe and guaranteed good image quality without significant differences when compared to gadobutrol and gadoteric acid in a wide range of CNS pathologies.

Introduction

The current suspension in Europe of certain linear gadolinium-based contrast agents (GBCAs) due to concern over the potential long-term consequences of retained gadolinium (Gd) in the brain [1] has led to the mandatory use of macrocyclic agents for all extra-hepatic magnetic resonance imaging procedures that require contrast enhancement. The decision of the European Medicines Agency (EMA) necessitated a switch away from the high relaxivity GBCA gadobenate dimeglumine (Bracco) for neuro MRI applications to gadobutrol (Gadovist; Bayer), gadoteric acid (Dotarem; Guerbet) or gadoteridol (ProHance; Bracco) [1]. These three macrocyclic GBCAs have similar rates of adverse events as determined in multi-centre, prospective, observational studies [2], [3], [4], [5], and similar r1 relaxivity values of approximately 4.6, 3.9 and 4.4 L•mmol−1•sec−1 (gadobutrol, gadoteric acid, gadoteridol, respectively, at 1.5 T) implying similar imaging performance [6]. However, whereas extensive real-word data are available for gadobutrol and gadoteric acid, much less was known about gadoteridol, particularly with regards to diagnostic performance in daily clinical routine.

The aim of our study was to prospectively evaluate the safety and efficacy of gadoteridol in a consecutive, non-selected and real world cohort of patients referred for contrast-enhanced MRI (CE-MRI) of the central nervous system (CNS) and to compare findings with a control group of patients that had undergone analogous contrast-enhanced neuro MRI examinations with either gadobutrol and gadoteric acid.

Section snippets

Patients

Between November 2017 and March 2018, 230 consecutive patients received gadoteridol for CE-MRI procedures. All 230 patients were prospectively included in the present analysis without any exclusions (Group 1).

All patients were evaluated for safety. A subset of patients (n = 130) with a truth standard diagnosis available was subsequently evaluated for diagnostic efficacy for the detection of malignancy and lesion characterisation.

Gold standard diagnoses were based on histology when available,

CE-MRI

All MR imaging was performed at 1.5 T (Philips Achieva dStream). The T1-weighted post-contrast scanning parameters varied with the neurological condition under investigation, as follows:

Brain: T1-weighted SE with TR/TE = 580ms/12ms, FA = 69°, section thickness = 5 mm, gap = 4 mm, Average 2; Spine: T1-weighted Dixon SE with TR/TE = 464ms/9ms, FA = 90°, section thickness = 4 mm, gap = 4.4 mm, Average 2; Orbit and paranasal sinus: TR/TE = 576ms/12ms, FA = 90°, section thickness = 3 mm, gap = 3.3 mm, Average 2. All post-contrast

Patients

A total of 460 patients (220 M/240F; mean age 54 ± 16 years) were enrolled. Group 1 comprised of 230 patients (112 M/118F; mean age 53 ± 17 years) that received gadoteridol while Group 2 comprised of 230 patients (108 M/122F; mean age 56 ± 15 years) that received either gadoteric acid (n = 83; 36.1%) or gadobutrol (n = 147; 63.9%). There were no significant differences between the two groups in terms of mean age or gender and no differences in terms of the distribution of neurological conditions (Table 1).

Discussion

To the best of our knowledge, this is the first prospective observational cohort study aimed at comparing gadoteridol with other macrocyclic GBCAs in terms of safety and diagnostic performance in an unrestricted patient population referred for CE-MRI for neurological conditions. We found that the safety and diagnostic efficacy of gadoteridol-enhanced MRI was comparable to that of MRI enhanced with gadoteric acid or gadobutrol across a range of CNS diseases (Fig. 3). Specifically, the

Conclusions

In conclusion, we have shown that there are no significant differences in terms of patient safety or diagnostic performance for the detection of malignant disease for patients administered gadoteridol compared to patients administered gadoteric acid or gadobutrol as part of routine clinical practice.

Ethics

Informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments.

Disclosure of interest

Nicoletta Anzalone is a speaker for Bayer, Guerbet and Bracco. The other authors declare that they have no competing interest.

Acknowledgements

We are really thankful to Miles Kirchin for language revision of the English text.

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