Johnson, SP;
Ogunlade, O;
Lythgoe, MF;
Beard, P;
Pedley, RB;
(2019)
Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors.
Clinical Cancer Research
, 25
(24)
pp. 7436-7447.
10.1158/1078-0432.CCR-19-0360.
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Ogunlade_Longitudinal photoacoustic imaging of the pharmacodynamic effect of vascular targeted therapy on tumors_AAM.pdf - Accepted Version Download (1MB) | Preview |
Abstract
PURPOSE: Photoacoustic imaging (PAI) is a novel non-invasive non-ionising 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 pathophysiological vascularisation were established as subcutaneous tumors in mice. Monitoring of response was performed over a 16-day 'regrowth' period following treatment at 40mg/kg, and at day 2 for a 'dose response' study at 40mg/kg, 10mg/kg, 1mg/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 vascularised 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 pathophysiological differences between patients has the potential to provide personalised drug therapy; we have demonstrated that PAI, which is clinically translatable, could be a powerful tool for this purpose.
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