Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of
adenoma development in the mouse model of
colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental
antitumor agent α-
difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory
drug sulindac during early [
chemoprevention (CP)] and late stages [
chemotherapy (CT)] of colon
tumorigenesis.
Biological endpoints for
drug interventions included OCT-generated
tumor number and
tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved
caspase-3,
cyclooxygenase (COX)-2, β-
catenin]. K-Ras
codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both
tumor number and
tumor burden for all experimental groups (P < 0.0001), but allows more accurate and full characterization of
tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with
sulindac suppressed both the
tumor number and
tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001) and K-RAS mutations frequency (P = 0.04). In the CT setting,
sulindac alone and DFMO/
sulindac combination were effective in reducing
tumor number, but not
tumor burden growth rate. A decrease in COX-2 staining in DFMO/
sulindac CT groups (COX-2, P < 0.01) confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of
tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring
colorectal cancer disease and effectiveness of
therapies in mouse models.