Innovative dual PET/NIRF tools for molecular imaging – M3ODALIty

Combined [18F]PET/NIRF imaging (Positron Emission Tomography/Near Infra Red Fluorescence) hold a huge potential to transform patient diagnosis and care. Such a combination conjugates the non-invasive whole-body diagnosis of PET with the intraoperative imaging-guided surgery or ex vivo histopathology of NIRF imaging. To implement this highly valuable dual imaging theranostic approach, adapted and smart imaging tools have urgently to be developed. M3ODALIty will design and synthesize two innovative dual [18F]PET/NIRF imaging dyes in addressing a double chemical and radiochemical challenge. A unique chemical structure will gather a cyanine derivative and fluorine-18 bound to a carbon center, and M3ODALIty will innovate in radiochemistry by the introduction of a “late stage” radiolabeling approach. Based on these dyes, original prototypes of MOnoMolecular Imaging Tools (MOMITs) for combined TEP/NIRF imaging will be elaborated. M3ODALIty ambitions as well to leverage the imaging options by the use, for the first time, of a bambusuril-scaffold allowing for a multivalent or multiplexed decoration with targeting entities. The modular character of the construction of the MOMITs will be a priority for a facile and exchangeable tuning of the targeting entities to address on demand a desired target. A proof of concept of these innovative MOMITs will be established in a robust and well validated model of angiogenesis using c(RGDfK) and A7R peptides targeting integrins and Neuropilin-1 receptors, respectively. Beyond the proof of concept, MOMITs developed within M3ODALIty will impact i) preclinical imaging in offering the possibility of a fluorescence-based cost-efficient in vitro screening of imaging candidates to select the optimal ones to be then used in vivo in combined TEP/NIRF, ii) clinical imaging in making a reality the combination of preoperative PET diagnosis followed by fluorescence imaging guided-surgery and iii) European SMEs involved in molecular imaging in proposing new potentially marketable imaging tools,. The monomolecular character of the imaging tools warrants an optimal translation from in vitro to in vivo. To implement these ambitious objectives, a consortium gathering specialists from the CEA and Université de Lorraine in macrocyclic and organic chemistry, radiochemistry, biology and imaging has been created. The researchers who will meet the challenges of MODALIty all have a free access to in-house or team-associated renowned radiochemistry and “state-of-the-art” preclinical PET and optical imaging facilities. M3ODALIty is rated 3/4 on Technological Readiness Level (TRL) for medical drugs and biologics with a strong translational potential to higher rates.