Longitudinal Photoacoustic Imaging Of The Pharmacodynamic Effect Of Vascular Targeted Therapy On Tumors

Purpose: Photoacoustic imaging (PAI) is a novel noninvasive and nonionizing imaging technique that allows longitudinal imaging of tumor vasculature in vivo and monitoring of response to therapy, especially for vascular targeted chemotherapy agents. In this study, we used a novel high-resolution all-optical PAI scanner to observe the pharmacodynamic response to the vascular-disrupting agent OXi4503.Experimental Design: Two models of colorectal carcinoma (SW1222 and LS174T) that possess differing pathophysiologic vascularization were established as subcutaneous tumors in mice. Monitoring of response was performed over a 16-day "regrowth" period following treatment at 40 mg/kg, and at day 2 for a "dose response" study at 40 mg/kg, 10 mg/kg, 1 mg/kg, and sham dose.Results: Qualitative and quantitative changes in PA signal are observed, with an initial decrease followed by a plateau and subsequent return of signal indicating regrowth. Both tumor types exhibited a decrease in signal; however, the more vascularized SW1222 tumors show greater response to treatment. Decreasing the dose of OXi4503 led to a decrease in PA signal intensity of 60%, 52%, and 20% in SW1222 tumors and 30%, 26%, and 4% for LS174T tumors.Conclusions: We have shown for the first time that PAI can observe the pharmacodynamic response of tumor vasculature to drug treatment both longitudinally and at different dose levels. Assessment of differing response to treatment based on vascular pathophysiologic differences among patients has the potential to provide personalized drug therapy; we have demonstrated that PAI, which is clinically translatable, could be a powerful tool for this purpose.