Targeting Brain Metastases with Ultrasmall Theranostic Nanoparticles, a First-in-human Trial from an MRI Perspective

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Aug 25

PMID 32832613

Citations 35

Authors

Camille Verry

Sandrine Dufort

Benjamin Lemasson

Sylvie Grand

Johan Pietras

Irene Tropres

Yannick Cremillieux

Francois Lux

Sebastien Meriaux

Benoit Larrat

Jacques Balosso

Geraldine Le Duc

Emmanuel L Barbier

Olivier Tillement

Affiliations

Soon will be listed here.

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.

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References

Fries P, Morr D, Muller A, Lux F, Tillement O, Massmann A . Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla. Rofo. 2015; 187(12):1108-15. DOI: 10.1055/s-0035-1553500. View

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

Verry C, Dufort S, Barbier E, Montigon O, Peoch M, Chartier P . MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. Nanomedicine (Lond). 2016; 11(18):2405-17. DOI: 10.2217/nnm-2016-0203. View

Le Duc G, Miladi I, Alric C, Mowat P, Brauer-Krisch E, Bouchet A . Toward an image-guided microbeam radiation therapy using gadolinium-based nanoparticles. ACS Nano. 2011; 5(12):9566-74. DOI: 10.1021/nn202797h. View

Stefancikova L, Lacombe S, Salado D, Porcel E, Pagacova E, Tillement O . Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells. J Nanobiotechnology. 2016; 14(1):63. PMC: 4964094. DOI: 10.1186/s12951-016-0215-8. View

Stefancikova L, Porcel E, Eustache P, Li S, Salado D, Marco S . Cell localisation of gadolinium-based nanoparticles and related radiosensitising efficacy in glioblastoma cells. Cancer Nanotechnol. 2014; 5(1):6. PMC: 4192560. DOI: 10.1186/s12645-014-0006-6. View

Le Duc G, Roux S, Paruta-Tuarez A, Dufort S, Brauer E, Marais A . Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment. Cancer Nanotechnol. 2015; 5(1):4. PMC: 4631720. DOI: 10.1186/s12645-014-0004-8. View

Lux F, Mignot A, Mowat P, Louis C, Dufort S, Bernhard C . Ultrasmall rigid particles as multimodal probes for medical applications. Angew Chem Int Ed Engl. 2011; 50(51):12299-303. DOI: 10.1002/anie.201104104. View

Miladi I, Aloy M, Armandy E, Mowat P, Kryza D, Magne N . Combining ultrasmall gadolinium-based nanoparticles with photon irradiation overcomes radioresistance of head and neck squamous cell carcinoma. Nanomedicine. 2014; 11(1):247-57. DOI: 10.1016/j.nano.2014.06.013. View

10.

Phillips E, Penate-Medina O, Zanzonico P, Carvajal R, Mohan P, Ye Y . Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med. 2014; 6(260):260ra149. PMC: 4426391. DOI: 10.1126/scitranslmed.3009524. View

11.

Bianchi A, Dufort S, Lux F, Courtois A, Tillement O, Coll J . Quantitative biodistribution and pharmacokinetics of multimodal gadolinium-based nanoparticles for lungs using ultrashort TE MRI. MAGMA. 2013; 27(4):303-16. DOI: 10.1007/s10334-013-0412-5. View

12.

Lin N, Lee E, Aoyama H, Barani I, Barboriak D, Baumert B . Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015; 16(6):e270-8. DOI: 10.1016/S1470-2045(15)70057-4. View

13.

Liauw S, Connell P, Weichselbaum R . New paradigms and future challenges in radiation oncology: an update of biological targets and technology. Sci Transl Med. 2013; 5(173):173sr2. PMC: 3769139. DOI: 10.1126/scitranslmed.3005148. View

14.

Singh Achrol A, Rennert R, Anders C, Soffietti R, Ahluwalia M, Nayak L . Brain metastases. Nat Rev Dis Primers. 2019; 5(1):5. DOI: 10.1038/s41572-018-0055-y. View

15.

Harrington K, Mohammadtaghi S, Uster P, Glass D, Peters A, Vile R . Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res. 2001; 7(2):243-54. View

16.

Retif P, Pinel S, Toussaint M, Frochot C, Chouikrat R, Bastogne T . Nanoparticles for Radiation Therapy Enhancement: the Key Parameters. Theranostics. 2015; 5(9):1030-44. PMC: 4493540. DOI: 10.7150/thno.11642. View

17.

Bonvalot S, Rutkowski P, Thariat J, Carrere S, Ducassou A, Sunyach M . NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial. Lancet Oncol. 2019; 20(8):1148-1159. DOI: 10.1016/S1470-2045(19)30326-2. View

18.

Mowat P, Mignot A, Rima W, Lux F, Tillement O, Roulin C . In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells. J Nanosci Nanotechnol. 2011; 11(9):7833-9. DOI: 10.1166/jnn.2011.4725. View

19.

Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann H . Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol. 2005; 40(11):715-24. DOI: 10.1097/01.rli.0000184756.66360.d3. View

20.

Sharma R, Plummer R, Stock J, Greenhalgh T, Ataman O, Kelly S . Clinical development of new drug-radiotherapy combinations. Nat Rev Clin Oncol. 2016; 13(10):627-42. DOI: 10.1038/nrclinonc.2016.79. View