THERAPROBES SIGNED

Project "THERAPROBES" data sheet

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 Project objective

Accurate diagnosis of (pre)malignant gastrointestinal (GI)-tract lesions is critical for patient survival. Early detection of asymptomatic disease of the GItract improves the chance of curative intervention by 50−80% as compared to poor five-year survival rates for symptomatic advanced malignant disease. Regular endoscopic surveillance in high-risk patients misses 25% of (pre)malignant lesions – the most clinically relevant marker for malignant progression. This clinically significant miss rate is due to the subtle appearance of such lesions under white-light endoscopy and sampling errors inherent to a random-biopsy surveillance paradigm, which increases inter-operator variability and compromises diagnostic accuracy. Even when malignant disease is detected, lack of sensitive contrast agents compromises delineation of the true extent of the lesion. These factors decrease the physician’s ability to achieve successful therapeutic intervention through resection or ablation. About 33% of GI-tract lesions progress or recur at or near the therapeutic site, commonly requiring aggressive yet often non-curative, systemic treatments negatively impacting the patients’ quality of life. There is an unmet clinical need for endoscopic optical imaging approaches that reliably detect those lesions with high sensitivity and specificity. To develop a clinically viable strategy, I propose to use biodegradable, fluorescent silica nanoprobes (FSN) that provide real-time visualization of the lesions over a range of scales during routine endoscopy. Since FSNs accumulate at the tumor sites solely due to their size and increased vascular permeability, no active targeting is needed, making these imaging agents ubiquitously applicable. Endoscopy augmented with FSNs has tremendous potential for better outcomes particularly in high-risk patients by accurately diagnosing and directing treatment specifically to early lesions at a time when patients are amenable to curative therapeutic intervention.