Developing new high relaxivity gadolinium-based contrast agents (GBCAs) for magnetic
resonance imaging (MRI) allowing dose reduction while maintaining similar diagnostic
efficacy is needed, especially in the context of gadolinium retention in tissues.
This study aimed to demonstrate that contrast-enhanced MRI of the central nervous
system (CNS) with gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1
mmol/kg, and superior to unenhanced MRI.PICTURE is an international, randomized, double-blinded,
controlled, cross-over, phase III study, conducted between June 2019 and September
2020. Adult patients with CNS lesions were randomized to undergo 2 MRIs (interval,
2-14 days) with gadopiclenol (0.05 mmol/kg) then gadobutrol (0.1 mmol/kg) or vice
versa. The primary criterion was lesion visualization based on 3 parameters (border
delineation, internal morphology, and contrast enhancement), assessed by 3 off-site
blinded readers. Key secondary outcomes included lesion-to-background ratio, enhancement
percentage, contrast-to-noise ratio, overall diagnostic preference, and adverse events.Of
the 256 randomized patients, 250 received at least 1 GBCA administration (mean [SD]
age, 57.2 [13.8] years; 53.6% women). The statistical noninferiority of gadopiclenol
(0.05 mmol/kg) to gadobutrol (0.1 mmol/kg) was achieved for all parameters and all
readers (n = 236, lower limit 95% confidence interval of the difference ≥-0.06, above
the noninferiority margin [-0.35], P < 0.0001), as well as its statistical superiority
over unenhanced images (n = 239, lower limit 95% confidence interval of the difference
≥1.29, P < 0.0001).Enhancement percentage and lesion-to-background ratio were higher
with gadopiclenol for all readers (P < 0.0001), and contrast-to-noise ratio was higher
for 2 readers (P = 0.02 and P < 0.0001). Three blinded readers preferred images with
gadopiclenol for 44.8%, 54.4%, and 57.3% of evaluations, reported no preference for
40.7%, 21.6%, and 23.2%, and preferred images with gadobutrol for 14.5%, 24.1%, and
19.5% (P < 0.001).Adverse events reported after MRI were similar for gadopiclenol
(14.6% of patients) and gadobutrol (17.6%). Adverse events considered related to gadopiclenol
(4.9%) and gadobutrol (6.9%) were mainly injection site reactions, and none was serious.Gadopiclenol
at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg for MRI of the CNS, confirming
that gadopiclenol can be used at half the gadolinium dose used for other GBCAs to
achieve similar clinical efficacy.
