Theragnostic Gadolinium-Based Nanoparticles Safely Augment X-ray Radiation Effects in Patients with Cervical Cancer

Cyrus Chargari, Pauline Maury, Matthieu Texier, Catherine Genestie, Philippe Morice, Sophie Bockel, Sébastien Gouy, Mouhamadou Ba, Samir Achkar, François Lux, Olivier Tillement, Sandrine Dufort, Géraldine L.E. Duc, Olivier Debeaumont, Christophe Massard, Amandine Maulard, Erika Porcel, Ratislav Bahleda, Samy Ammari, Daphné MorelSophie Espenel, Patricia Pautier, Charlotte Robert, Eric Deutsch

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    2 Citations (Scopus)

    Abstract

    Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This “theragnostic” action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.

    Original languageEnglish
    Pages (from-to)16516-16529
    Number of pages14
    JournalACS Nano
    Volume18
    Issue number26
    DOIs
    Publication statusPublished - 2 Jul 2024

    Keywords

    • brachytherapy
    • cervical cancer
    • gadolinium-based nanoparticles
    • phase I
    • radiation oncology
    • radiotherapy
    • theragnostics

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