Photoacoustic imaging of integrin-overexpressing tumors using a novel ICG-based contrast agent in mice

Martina Capozza, Francesco Blasi, Giovanni Valbusa, Paolo Oliva, Claudia Cabella, Federica Buonsanti, Alessia Cordaro, Lorena Pizzuto, Alessandro Maiocchi, Luisa Poggi
PhotoAcoustic Imaging (PAI) is a biomedical imaging modality currently under evaluation in preclinical and clinical settings. In this work, ICG is coupled to an integrin binding vector (ICG-RGD) to combine the good photoacoustic properties of ICG and the favourable αvβ3-binding capabilities of a small RGD cyclic peptidomimetic. ICG-RGD is characterized in terms of physicochemical properties, biodistribution and imaging performance. Tumor uptake was assessed in subcutaneous xenograft mouse models of human glioblastoma (U-87MG, high αvβ3expression) and epidermoid carcinoma (A431, low αvβ3expression). ICG and ICG-RGD showed high PA signal in tumors already after 15 min post-injection. At later time points the signal of ICG rapidly decreased, while ICG-RGD showed sustained uptake in U-87MG but not in A431 tumors, likely due to the integrin-mediated retention of the probe. In conclusion, ICG-RGD is a novel targeted contrast agents for PAI with superior biodistribution, tumor uptake properties and diagnostic value compared to ICG.

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