Research ArticleHEALTH AND MEDICINE

Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective

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Science Advances  15 Jul 2020:
Vol. 6, no. 29, eaay5279
DOI: 10.1126/sciadv.aay5279
  • Fig. 1 Contrast-enhanced MRI and SE mapping.

    First and second row images are obtained pre/postadministration of Gd-based nanoparticles using three-dimensional (3D) T1-weighted imaging sequence. The green arrows are pointing highlighted metastases. Third row images are corresponding SE maps with conspicuous local increase of intensity (light blue to orange color) in all different types of brain metastases. The fourth row shows a 3D visualization of all metastases with SE.

  • Fig. 2 MRI SE in observable brain metastases (longest diameter greater than 1 cm).

    (A) MRI SE as a function of the injected dose of AGuIX nanoparticle. Each point corresponds to an MRI SE value measured in a metastasis for all patients. Mean value and SD (error bar) are displayed. The solid line and the equation correspond to the linear regression on the mean values. BW, body weight. (B) MRI SE by primary tumor type. Each point corresponds to an SE value, normalized to the administered AGuIX dose, measured in a metastasis for all patients. Mean value and SD (error bar) are displayed. NSCLC, non–small-cell lung carcinoma. (C) MRI SE as a function of the longest diameter of metastases for each type of primary tumor. Each point corresponds to an SE value, normalized to the administered AGuIX dose, measured in a metastasis for all patients.

  • Fig. 3 Comparative enhancement of MRI signal following administration of AGuIX and Dotarem.

    (A) Each point corresponds to an MRI SE value measured in a metastasis for patients receiving 100 mg/kg body weight AGuIX dose. The solid lines and the equations correspond to the linear regressions for each primary tumor type (e.g., NSCLC and breast cancer). (B) Correlation between MRI SE and AGuIX concentration following AGuIX administration. Each point corresponds to an MRI SE and AGuIX concentration value measured in a metastasis of patients #13, #14, and #15 injected with a 100 mg/kg body weight AGuIX dose. The solid lines correspond to the linear regression applied to the series of points.

  • Fig. 4 MRI SE 1 week after the administration of nanoparticles.

    3D visualization of patients brain superimposed with color-encoded SE in NSCLC metastases 2 hours p.i. (postinjection) on the left and 7 days p.i. on the right. The patient was administered with the largest dose of nanoparticles (100 mg/kg body weight).

  • Fig. 5 AGuIX theranostic nanoparticle.

    (A) Schematic representation of AGuIX nanoparticles. DOTA(Gd) species are grafted to the polysiloxane core (Si, pearl gray; O, red; C, gray; N, blue; Gd, metallic blue; and H, white). (B) Main properties of AGuIX nanoparticle. (C) Hydrodynamic diameter distribution of AGuIX nanoparticles as obtained by dynamic light scattering. (D) Zeta potential of AGuIX nanoparticle as a function of the pH.

  • Fig. 6 Timeline of the NanoRad clinical trial.

    At day 0 (D0), the patients underwent an MRI session with injection of Dotarem. At D1, the patients received a single intravenous (IV) injection of AGuIX nanoparticles. Two hours later, the patients underwent an MRI session. After 2 more hours, the patients received their first session of whole-body radiation therapy (WBRT; 30 Gy split in 10 fractions). Further MRI sessions were performed at D8 (no Dotarem injection), D28 (Dotarem injection), month 3 (M3), and then every 3 months for 12 months (Dotarem injection).

Supplementary Materials

  • Supplementary Materials

    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 Troprès, Yannick Crémillieux, François Lux, Sébastien Mériaux, Benoit Larrat, Jacques Balosso, Géraldine Le Duc, Emmanuel L. Barbier, Olivier Tillement

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