Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study)

Abstract

Background and purpose: Gadobutrol (Gadavist) and gadoteridol (ProHance) have similar macrocyclic molecular structures, but gadobutrol is formulated at a 2-fold higher (1 mol/L versus 0.5 mol/L) concentration. We sought to determine whether this difference impacts morphologic contrast-enhanced MR imaging.

Materials and methods: Two hundred twenty-nine adult patients with suspected or known brain tumors underwent two 1.5T MR imaging examinations with gadoteridol or gadobutrol administered in randomized order at a dose of 0.1 mmol/kg of body weight. Imaging sequences and T1 postinjection timing were identical for both examinations. Three blinded readers evaluated images qualitatively and quantitatively for lesion detection and for accuracy in characterization of histologically confirmed brain tumors. Data were analyzed by using the Wilcoxon signed rank test, the McNemar test, and a mixed model.

Results: Two hundred nine patients successfully completed both examinations. No reader noted a significant qualitative or quantitative difference in lesion enhancement, extent, delineation, or internal morphology (P values = .69-1.00). One hundred thirty-nine patients had at least 1 histologically confirmed brain lesion. Two readers found no difference in the detection of patients with lesions (133/139 versus 135/139, P = .317; 137/139 versus 136/139, P = .564), while 1 reader found minimal differences in favor of gadoteridol (136/139 versus 132/139, P = .046). Similar findings were noted for the number of lesions detected and characterization of tumors (malignant/benign). Three-reader agreement for characterization was similar for gadobutrol (66.4% [κ = 0.43]) versus gadoteridol (70.3% [κ = 0.45]). There were no significant differences in the incidence of adverse events (P = .199).

Conclusions: Gadoteridol and gadobutrol at 0.1 mmol/kg of body weight provide similar information for visualization and diagnosis of brain lesions. The 2-fold higher gadolinium concentration of gadobutrol provides no benefit for routine morphologic imaging.

Fig 1.

Flow chart outlining patient enrollment, drop-out rates, and lesion study populations.

Fig 2.

Bar graphs show reader preference and diagnostic results from 3 independent blinded readers for the following: global diagnostic preference (A), border delineation (B), internal morphology (C), lesion extent (D), and qualitative contrast enhancement (E). Comparisons are based on 198 patients for reader 1, 194 patients for reader 2, and 196 patients for reader 3. Each reader expressed no preference for either agent in the overwhelming number of cases for all 5 assessments. The small number of cases in which 1 agent is preferred is nearly equally distributed for gadobutrol versus gadoteridol. Note the very high reader agreement for all measures.

Fig 3.

A 61-year-old man with brain metastases from primary lung cancer. Images were acquired before (A, unenhanced T1 SE) and after (B, T1 SE; C, high-resolution T1 GRE) administration of gadoteridol and before (D, unenhanced T1 SE) and after (E, T1 SE; F, high-resolution T1 GRE) administration of gadobutrol. Two lesions clearly seen in both examinations show no differences in contrast enhancement or in the size of lesions.

Fig 4.

A 51-year-old woman with glioblastoma multiforme. Images were acquired before (A, unenhanced T1 SE) and after (B, T1 SE; C, high-resolution T1 GRE) administration of gadoteridol and before (D, unenhanced T1 SE) and after (E, T1 SE; F, high-resolution T1 GRE) administration of gadobutrol. A rim-enhancing mass in the right thalamus with extension into the posterior interhemispheric region is clearly seen in both examinations. No differences in contrast enhancement or in the size of lesions are apparent.

Fig 5.

Blinded reader comparison of mean postcontrast-precontrast lesion-to-background ratio on T1 SE sequences after 0.1-mmol/kg doses of gadoteridol and gadobutrol. No significant differences were noted by any reader.