Magnetic resonance imaging-based biodistribution of theranostic AGuIX nanoparticles in the NANORAD 2 clinical trial for brain metastases

Purpose 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). Methods Signal enhancement (SE) maps were generated from T1-weighted MRI scans of 11 patients receiving AGuIX injections prior to radiotherapy. SE values were measured in 14 regions of interest at one and four hours post-injection across three administrations to evaluate nanoparticle retention and clearance dynamics. Results At one hour post-injection, SE was significantly elevated in brain metastases (median 78.1%, IQR: 51.5%-108.7%, n = 208), while healthy brain tissue showed no detectable SE. At four hours, metastatic SE decreased by a median of 33.2% (n = 54), indicating partial clearance. Surrounding organs exhibited transient SE (e.g., pituitary gland: median 73.1%, n = 11) that significantly declined at four hours. After three injections, metastatic SE remained stable (63.0%-64.8%, n = 132), suggesting complete clearance between administrations. Conclusion This study confirms selective AGuIX accumulation in brain metastases, supporting their role in targeted radiotherapy. The clearance dynamics justify delivering radiotherapy four hours post-injection, with no cumulative accumulation observed after three administrations.