Near-Infrared Fluorescent Activated Polymeric Probe for Imaging Intraluminal Colorectal Cancer Tumors.

Detection and removal of preneoplastic tumors is crucial for successful colorectal cancer (CRC) therapy. Here we describe the design of a Cathepsin B (CB)-activated polymeric probe, P-(GGFLGK-IR783), for imaging CRC tumors established by intrarectal or subcutaneous (s.c.) implantation of human colon cancer cells (SW-480 and HT-29) in mice. Multiple copies of the near-infrared fluorescent (NIRF) dye IR783 were attached to a single HPMA copolymer backbone via a CB-cleavable linker (GFLG), and the influence of the dye loading on the fluorescence quenching and activation by CB was assessed in vitro, ex vivo, and in vivo. The optimal dose and dosing regimen of P-(GGFLGK-IR783) for colonic tumor detection was determined. Increasing the IR783 loading in the copolymer from 2.5 to 20 mol % resulted in quenching of the fluorescence signal that was activated in vitro by the action of CB from different origins. Following intravenous administration, P-(GGFLGK-IR783)7.5% preferentially accumulated in intrarectal and s.c. implanted tumors, allowing tumor visualization after 4 h and even 48 h postadministration. Activation of P-(GGFLGK-IR783)7.5% by CB was clearly detected in s.c. implanted tumors, revealing about a 4-fold increase in the fluorescence signal in tumors vs healthy colon tissue. The probe containing the CB-cleavable linker produced higher fluorescence signal intensity in tumors, relative to the noncleavable probe. These results indicate that P-(GGFLGK-IR783)7.5% may aid in detecting CRC tumors and can help to guide selective removal of polyps during colonoscopic procedures.

New optical method for enhanced detection of colon cancer by capsule endoscopy.

PillCam®COLON capsule endoscopy (CE), a non-invasive diagnostic tool of the digestive tract, has dramatically changed the diagnostic approach and has become an attractive alternative to the conventional colonoscopy for early detection of colorectal cancer. However, despite the significant progress and non-invasive detection capability, studies have shown that its sensitivity and specificity is lower than that of conventional colonoscopy. This work presents a new optical detection method, specifically tailored to colon cancer detection and based on the well-known optical properties of immune-conjugated gold nanorods (GNRs). We show, on a colon cancer model implanted in a chick chorioallantoic membrane (CAM), that this detection method enables conclusive differentiation between cancerous and normal tissues, where neither the distance between the light source and the intestinal wall, nor the background signal, affects the monitored signal. This optical method, which can easily be integrated in CE, is expected to reduce false positive and false negative results and improve identification of tumors and micro metastases.