Ultrasound is a powerful technique for medical imaging. However, the short lifetime and large size of the gas-filled microbubbles used as clinical contrast agents limits its use for long-term applications and, in particular, for tracking of cellular therapies. Recently, 19F MRI, has become an established technique for cell imaging. It provides direct quantification of cell numbers by imaging the 19F nuclei inside the contrast agent. Using the same contrast agent for both techniques could streamline the imaging process and enable fast screening with ultrasound along with quantification by 19F MRI.
This study revealed that nanoparticles consisting of a liquid perfluorocarbon and biodegradable polymer are suitable for imaging with both 19F MRI and ultrasound techniques. They remain stable for more than 48 hours during repeat ultrasound imaging sessions and, unlike microbubble-based contrast agents, they can enter the therapeutic immune cells without damaging them.
Due to the small size and high stability of the nanoparticles, the mechanism behind their visibility using ultrasound was not clear. Small angle neutron scattering measurements provided the researchers with an important insight. They found that the nanoparticles had an internal structure atypical for perfluorocarbon-loaded nanoparticles that could potentially explain the unusual imaging characteristics. The nanoparticles contain 12 nm core-shell building blocks, inside which highly hydrophobic perfluorocarbon was hydrated.
These nanoparticles provide exciting prospects for long-term imaging with ultrasound and 19F MRI. They can be further tailored to other imaging or therapeutic applications, and could aid the movement towards personalised medication and the desired flexibility in clinical imaging. These nanoparticles are translatable to humans and have been approved for a pilot clinical trial. The research has also led to the foundation of a spin-out company, Cenya Imaging B.V.
Related publication: “Multicore Liquid Perfluorocarbon‐Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking” Advanced Functional Materials, 29, 19 (2019)
Funding: Netherlands Organization for Scientific Research, European Research Council, Netherlands Institute of Regenerative Medicine, EU FP7 program ENCITE and NanoNextNL.
Authors: O Koshkina (Radboud Institute for Molecular Life Sciences, Max Planck Institute for Polymer Research), G Lajoinie (University of Twente), F Baldelli Bombelli (Politecnico di Milano), E Swider (Radboud Institute for Molecular Life Sciences), LJ Cruz (Leiden University Medical Centre), PB White (Radboud University), R Schweins (ILL), Y Dolen, EAW van Dinther, NK van Riessen (Radboud Institute for Molecular Life Sciences), SE Rogers (ISIS), R Fokkink (Wageningen University), IK Voets (Eindhoven University of Technology), ERH van Eck (Radboud University), A Heerschap (Radboudumc), M Versluis (University of Twente), CL de Korte (University of Twente, Radboudumc), CG Figdor, IJM de Vries, M Srinivas (Radboud Institute for Molecular Life Sciences)