Hybrid Nano-GdF3 contrast media allows pre-clinical in vivo element-specific K-edge imaging and quantification

Niki Halttunen,Frederic Lerouge,Monica Sigovan,Emmanuel Chereul,Stephane Parola,Loic Boussel,Philippe Douek,Frederic Chaput,Szilvia Karpati,Marc Vandamme,Salim Si-Mohamed

doi:10.1038/s41598-019-48641-z

Abstract

Computed tomography (CT) is a widely used imaging modality. Among the recent technical improvements to increase the range of detection for optimized diagnostic, new devices such as dual energy CT allow elemental discrimination but still remain limited to two energies. Spectral photon-counting CT (SPCCT) is an emerging X-ray imaging technology with a completely new multiple energy detection and high spatial resolution (200 μm). This unique technique allows detection and quantification of a given element thanks to an element-specific increase in X-ray absorption for an energy (K-band) depending on its atomic number. The main contrast media used hitherto are iodine-based compounds but the K-edge of iodine (33.2 keV) is out of the range of detection. Therefore, it is crucial to develop contrast media suitable for this advanced technology. Gadolinium, well known and used element for MRI, possess a K-edge (50.2 keV) well suited for the SPCCT modality. The use of nano-objects instead of molecular entities is pushed by the necessity of high local concentration. In this work, nano-GdF3 is validated on a clinical based prototype, to be used as efficient in vivo contrast media. Beside an extremely high stability, it presents long lasting time in the blood pool allowing perfusion imaging of small animals, without apparent toxicity.

Highlights

Since its introduction over 40 years ago[1,2], Computed tomography (CT) has become one of the most used imaging modalities with MRI for clinical purposes in hospitals, especially in the emergency room
Gadolinium is an element with a k-edge of 50.2 keV, which is within the detection range of the X-ray tube emission
Transmission electron microscopy (TEM) and dynamic light scattering (DLS) showed that the nanocrystals exhibited an average size of about 10 nm with a low polydispersity and a hydrodynamic diameter centred at 14 nm

Summary

Introduction

Since its introduction over 40 years ago[1,2], CT has become one of the most used imaging modalities with MRI for clinical purposes in hospitals, especially in the emergency room. Gadolinium is an element with a k-edge of 50.2 keV, which is within the detection range of the X-ray tube emission This element is already well known and used for its magnetic properties as contrast media for MRI under its Gd3+ cage-complex form (DOTAREM, GADOVIST) in clinics or nanoparticles in research developments[19,20]. We discuss the preparation and in vivo evaluation of ultra-small GdF3 nanocrystals as stable efficient contrast media for angiography with SPCCT clinical prototype suitable for preclinical studies, with a biodistribution study on mice and K-edge imaging on rats These nanoparticles present two main advantages compared to the organometallic gadolinium complexes. These systems provide a very high local density of active ions, making them efficient probes for various imaging modalities

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