Double-Dose Gadopiclenol Improves Detection of Small Brain Metastases

Because gadopiclenol’s high relaxivity allows it to be approved at half the dose used for other macrocyclic MRI contrast agents, Josef Vymazal, MD, and colleagues designed a randomized study to test whether using a higher, off-label dose of the agent, equivalent to the standard dose used for other contrast agents, would improve detection of small brain metastases relative to the recommended half dose.

In an interview with CancerNetwork® at the 2026 SNO/ASCO CNS Metastases Conference, Vymazal described the design and outcome of that study. All patients first received a standard postcontrast dose of gadopiclenol (0.05 mmol/kg), with delayed imaging performed roughly 13 minutes later. At that point, patients were divided so that half received an additional dose of gadopiclenol prior to the delayed imaging, constituting a delayed double dose (DDD; 0.1 mmol/kg total; n=81), while the remaining subjects did not receive a second dose, constituting a delayed single dose (DSD; n=78).

Across the full cohort, readers identified 1035 consensus-detected lesions and 1335 majority-detected lesions, with a median consensus lesion diameter of 7 mm (IQR, 4-15) and 41% of consensus lesions measuring 5 mm or smaller. DDD imaging detected significantly more consensus lesions than standard, non-delayed imaging (255 vs 215; P <.001), while DSD imaging did not produce a significant difference (287 vs 278; P =.48). The DDD upstaging-to-downstaging ratio was 2.9:1, compared with 1.1:1 for DSD. The detection advantage with DDD was driven predominantly by small lesions, with 79% of additional majority-detected lesions on DDD scans measuring 5 mm or smaller. The lesion-to-normal-appearing white matter signal ratio increased by 18% on DDD scans (from 1.83 to 2.13; P <.001) but was unchanged with DSD (P =.70). The benefit of DDD imaging was consistent across all 3 readers, with no significant reader-by-dose interaction.

Vymazal described these results in terms of their direct, practical consequence for radiosurgery planning, where identifying the full burden of metastatic disease informs how many lesions can be targeted in a single treatment session.

Vymazal is head of the Department of Radiology and deputy director for Science and Research at Faculty Hospital Motol and Homolka, and a full professor at Charles University in Prague, Czech Republic.

Transcript:

CancerNetwork: How was this study designed, and what did you find?

Vymazal: We designed our study so that we divided patients in a random way—A-B-A-B-A-B—with a single dose, which is the…recommended half dose, and then, off-label—of course, the patients signed informed consent and so on—with the double dose, which is in fact not a double dose. It’s a standard dose for other contrast agents. The question was: did we detect more metastatic lesions with the…double dose in comparison with the half dose of this contrast agent. The result was statistically significant. We scanned 159 patients, divided randomly into 2 groups, and there is a statistical increase in detecting small metastatic lesions with the double dose—that is, the standard dose for other MR contrast agents. The increase is quite significant. In every second patient, more or less, statistically speaking, one more lesion [was found]. The practical consequence is clear for radiosurgery.

Reference

Vymazal J, Ryznarova Z, Keller J, Liscak R, Rulseh A. Comparison of delayed and double-dose MRI for detection of brain metastases with gadopiclenol prior to stereotactic radiosurgery. Neurooncol Adv. 2026;8(Suppl 6):vdag161.062. doi:10.1093/noajnl/vdag161.062