Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective
Camille Verry, Sandrine Dufort, Benjamin Lemasson, Sylvie Grand, Johan Pietras, Irène Troprés, Yannick Crémillieux, François Lux, Sébastien Mériaux, Benoît Larrat, Jacques Balosso, Géraldine Le Duc, Emmanuel Barbier, Olivier Tillement
Abstract
The use of radiosensitizing nanoparticles with both imaging and therapeutic properties on the same nano-object is regarded as a major and promising approach to improve the effectiveness of radiotherapy. Here, we report the MRI findings of a phase 1 clinical trial with a single intravenous administration of Gd-based AGuIX nanoparticles, conducted in 15 patients with four types of brain metastases (melanoma, lung, colon, and breast). The nanoparticles were found to accumulate and to increase image contrast in all types of brain metastases with MRI enhancements equivalent to that of a clinically used contrast agent. The presence of nanoparticles in metastases was monitored and quantified with MRI and was noticed up to 1 week after their administration. To take advantage of the radiosensitizing property of the nanoparticles, patients underwent radiotherapy sessions following their administration. This protocol has been extended to a multicentric phase 2 clinical trial including 100 patients.