AGuIX nanoparticles are promising theranostic agents that selectively accumulate in brain metastases via the enhanced permeability and retention effect, potentially improving radiotherapy efficacy. This ancillary analysis of the NANORAD2 trial investigates AGuIX biodistribution in patients with multiple brain metastases undergoing whole-brain radiotherapy (WBRT). Signal enhancement (SE) maps, quantifying the relative increase in T1-weighted MRI signal intensity due to AGuIX accumulation, were generated from pre- and post-injection scans of 11 patients receiving three weekly AGuIX injections (100 mg/kg) prior to radiotherapy. SE values were measured in 14 regions of interest at one hour post-injection in all patients (n = 11), at four hours in a subset (n = 4) to assess early clearance, and at one hour after the third injection (n = 7) to evaluate long-term accumulation. At one hour post-first injection, full-volume brain metastases showed marked SE elevation to 54.1 ± 29.5% (mean and standard deviation, n = 208 metastases), while surrounding organs exhibited transient SE (especially pituitary gland) that declined at four hours (all SE values < limit of detection, n = 11). At four hours, mean metastatic SE decreased from 33.8 ± 18.4% to 18.8 ± 16.6% (n = 54, p < 10− 10), indicating partial clearance. After three weekly injections, mean metastatic SE at one hour remained stable comparing to first injection (from 63.0% to 64.8%, n = 132), demonstrating complete inter-dose clearance with no cumulative accumulation detectable by MRI. This study confirms selective AGuIX accumulation in brain metastases with favorable clearance kinetics, supporting radiotherapy delivery four hours post-injection to optimize therapeutic ratio while minimizing off-target exposure.
Boux et al. (Wed,) studied this question.