Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract

Background: Current capsule endoscopy (CE) provides minimally invasive technology for GI imaging but has limited ability to discriminate different types of polyps. Near infrared fluorescent (NIRF) probes activated by biomarkers upregulated in adenomas (eg, cathepsin B) are potentially powerful tools to distinguish premalignant or malignant lesions from benign or inflammatory lesions. Objectives: To examine whether CE can be integrated with NIRF probes to detect adenomas and whether cathepsin B-activated NIRF probes are activated by benign or inflammatory Design: Mouse models of adenomas, hyperplactic/lymphoid polyps, and acute or chronic intestinal inflammation were injected intravenously with a cathepsin B-activated probe (Prosense 680). Dissected intestine was imaged with CE under white or NIRF light. For NIRF excitation (680 nm), dichroic and emission (700 nm) filters were combined with CE when images were recorded. Prosense 680 samples with or without protease were used as positive and negative controls. CE-based imaging data were verified by using and independent imaging system (Xenogen IVIS system). Main Outcome Measurements: Proof of principal that CE integrated with NIRF probes can detect and discriminate adenomas from other lesions. Results: CE-based NIRF imaging with Prosense 680 readily visualized adenomas, including in the colitis model. NIRF signals of different intensities were detected. Prosense 680 was not activated by benign or inflammatory lesions. Limitation: Optical filters external to the capsule were used. Conclusions: We demonstrate proof of the principle that biochromoendoscopy-CE combined with molecular probes-provides a novel approach that differentiates adenomas from beningn polyps and inflammatory lesions.