We are investigating an imaging agent for early detection of
colorectal cancer. The agent, named the nanobeacon, is
coumarin 6-encapsulated
polystyrene nanospheres whose surfaces are covered with
poly(N-vinylacetamide) and
peanut agglutinin that reduces non-specific interactions with the normal mucosa and exhibits high affinity for terminal
sugars of the
Thomsen-Friedenreich antigen, which is expressed
cancer-specifically on the mucosa, respectively. We expect that
cancer can be diagnosed by detecting illumination of intracolonically administered nanobeacon on the mucosal surface. In the present study, biopsied human tissues were used to evaluate the potential use of the nanobeacon in the clinic. Prior to the clinical study, diagnostic capabilities of the nanobeacon for detection of
colorectal cancer were validated using 20 production batches whose characteristics were fine-tuned chemically for the purpose. Ex vivo imaging studies on 66 normal and 69
cancer tissues removed from the colons of normal and orthotopic mouse models of human
colorectal cancer, respectively, demonstrated that the nanobeacon detected
colorectal cancer with excellent capabilities whose rates of true and false positives were 91% and 5%, respectively. In the clinical study, normal and
tumor tissues on the large intestinal mucosa were biopsied endoscopically from 11 patients with
colorectal tumors. Histological evaluation revealed that 9 patients suffered from
cancer and the rest had
adenoma. Mean fluorescence intensities of
tumor tissues treated with the nanobeacon were significantly higher than those of the corresponding normal tissues. Correlation of magnitude relation of the intensity in individuals was observed in
cancer patients with a high probability (89%); however, the probability reduced to 50% in
adenoma patients. There was a reasonable likelihood for diagnosis of
colorectal cancer by the nanobeacon applied to the mucosa of the large intestine.