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Clinical ultrasound platform for the quantitative and longitudinal imaging of theranostics and cellular therapy (CoNQUeST)
Date du début: 1 avr. 2014, Date de fin: 31 mars 2018 PROJET  TERMINÉ 

The success of modern medical treatments such as cellular therapy and targeted treatments requires appropriate tools for in vivo monitoring. Imaging modalities, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) are key candidates due to their noninvasive nature. However, these imaging techniques are extremely expensive and can involve radiation, both of which hinder their longitudinal and repetitive use.Ultrasound has so far been unsuitable due to the absence of a label to differentiate regions of interest from tissue background, the main problem being that current ultrasound contrast agents (CAs) have active lifetimes in the order of minutes. The CoNQUeST platform (Clinical Nanoparticles for Quantitative Ultrasound with high STability) proposed here is an entirely new type of ultrasound CA that is extremely stable (lifetime of a year) and is not affected by insonation. This mechanism of contrast generation appears completely novel: The polymeric particles are under 200nm in diameter and must contain a soluble metal (M.Srinivas et al., patent pending, filed 09/2012). Based on the current state of the art, these particles are too small and do not contain the requisite gaseous component for ultrasound contrast.CoNQUeST particles are applicable to longitudinal and repeated imaging, as is necessary for cell tracking, due to their stability. Furthermore, these particles can be chemically bound to targeting agents, dyes and drugs, and are suitable for multimodal imaging, including MRI (both 1H and 19F), fluorescence and SPECT. Finally, the CoNQUeST agents are suitable for clinical use.I propose the application of the CoNQUeST agents to a clinical trial for tracking dendritic cell therapy in melanoma patients, longitudinal theranostic imaging in preclinical models and thorough characterisation of this novel mechanism of ultrasound contrast generation.