Size-dependent Tumor Response to Photodynamic Therapy and Irinotecan Monotherapies Revealed by Longitudinal Ultrasound Monitoring in an Orthotopic Pancreatic Cancer Model

Longitudinal monitoring of tumor size in vivo can provide important biological information about disease progression and treatment efficacy that is not captured by other modes of quantification. Ultrasound enables high-throughput evaluation of orthotopic mouse models via fast acquisition of three-dimensional tumor images and calculation of volume with a reasonable degree of accuracy. Herein, we compare orthotopic pancreatic tumor volume measurements determined by ultrasound with volume measured by calipers and tumor weight, and found strong correlations between the three modalities over a large range of tumor sizes, suggesting ultrasound can accurately quantify tumor volumes in this model. Furthermore, we demonstrate the unique ability of longitudinal treatment monitoring to reveal a tumor size-dependent response to Benzoporphyrin Derivative photodynamic therapy (BPD-PDT) and irinotecan. Small tumors (5-35 mm(3)) were found to respond well to a single round of PDT, while large tumors (35-65 mm(3)) showed no response to the same treatment. These results highlight the role that tumor size can play in preclinical interpretation of treatment response and more generally suggest that careful evaluation of subtle biological features such as this must be carefully considered in order to grant a more comprehensive understanding of disease biology in vivo.