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Perfluorooctyl Bromide Polymeric Capsules as Dual Contrast Agents for Ultrasonography and Magnetic Resonance Imaging

Authors


  • Authors would like to thank D. Jaillard and J. Degrouard (CCME, Orsay) for TEM experiments, A. Allavena-Valette (CECM, Vitry sur Seine) for access to the SEM facility, V. Nicolas (IFR 141, ITFM) for confocal microscopy, P. Laugier for fruitful discussions, L. Harivardhan Reddy for help with animals, and G. Barratt for carefully proofreading the manuscript. Authors acknowledge financial support from ANR (Agence Nationale de la Recherche, NT05-3_42548), in particular for fellowships to E.P. and N.T. This study was funded in part by the EC – FP6-project DiMI, LSHB-CT-2005-512146.

Abstract

Polymeric capsules with a thick shell made of biodegradable and biocompatible polymer and a liquid core of perfluorooctyl bromide (PFOB) were evaluated for stability as well as for ultrasound and magnetic resonance imaging (MRI) contrast enhancement. The method of preparation allows the mean capsule diameter to be regulated between 70 nm and 25 µm and the capsule thickness-to-radius ratio from 0.25 to 0.54. Capsule diameter remains stable at 37 °C in phosphate buffer for at least 4 and 6 h for nanocapsules and microcapsules, respectively. The in vitro ultrasound signal-to-noise ratio (SNR) was measured from 40 to 60 MHz for 6 µm and 150 nm capsules: the SNR increases with capsule concentration up to 20–25 mg mL−1, and then reaches a plateau that depends on capsule diameter (13.5 ± 1.5 dB for 6 µm and 6 ± 2 dB for the 150 nm capsules). The ultrasound SNR is stable for up to 20 min for microcapsules and for several hours for nanocapsules. For nanocapsules, the thinner the shell, the larger the SNR and the more compressible the capsules. Nanocapsule suspensions imaged in vitro with a commercial ultrasound imaging system (normal and tissue harmonic imaging modes, 7–14 MHz probe) were detected down to concentrations of 12.5 mg mL−1. Injections of nanocapsules (200 µg ml−1) in mice in vivo reveal that the initial bolus passage presents significant ultrasound enhancement of the blood pool during hepatic imaging (7–14 MHz probe, tissue harmonic imaging mode). 19F-MRI images were obtained in vitro at 9.4T using spin-echo and gradient echo sequences and allow detecting nanocapsules in suspension (50 mg mL−1). In conclusion, these results show initial feasibility for development of these capsules toward a dual-modality contrast agent.

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