Abstract 5211: In vivo fluorescence and spectral microscopy of the effects of aerobic exercise on tumor oxygenation and perfusion in breast cancer

Abstract

Abstract Abnormal tumor angiogenesis leads to inefficient blood flow and inhibited delivery of oxygen, resulting in a hypoxic tumor microenvironment. In radiation therapy the presence of oxygen is necessary to impart lasting damage to cancer cells, therefore the modulation of tumor hypoxia has been an important focus to improve radiation therapy outcome. While strategies such as hyperbaric chambers and hypoxic cell radiosensitizers or cytotoxins have shown merit, their success in the clinic has been limited. A potential method to increase oxygenation and decrease hypoxia in a tumor mass that is safe and well-tolerated is aerobic exercise. For cancer patients, the benefits of exercise in a palliative setting are well known, however the effects of exercise on tumor microvasculature and blood flow have not been extensively characterized. In vivo microscopy of microvessel function in preclinical models is a useful tool for the study of tumor vascular structure and function. The combination of hyperspectral imaging of hemoglobin (Hb) saturation and first-pass fluorescence (FPF) imaging of blood transit time in the murine dorsal skinfold window chamber has been previously used to characterize tumor angiogenesis, wound healing and the response of tumor microvasculature to vascular targeting agents. Hb saturation imaging reveals the oxygenation of blood within microvessels while FPF imaging gives information regarding blood flow and network connections by recording a fluorescent contrast agent as it is injected into circulation. In the present study, this combination imaging technique is used to evaluate the impact of treadmill running on tumor blood flow and microvessel oxygenation in real time. 4T1 mammary tumors were initiated in nude mice bearing titanium window chambers. Once tumors reached a volume of ∼5mm3, mice were subjected to daily treadmill running for 5-7 consecutive days (30 min, 15-18 m/min, 10° incline). As a sedentary control, mice were placed on a stationary treadmill for equivalent periods of time. Combination imaging was performed daily to monitor microvessel oxygenation and blood flow. On the first day of exercise, imaging was performed both before and after animals were exercised. Preliminary results indicate that following one bout of exercise, tumor perfusion is increased, however there was no significant correlation between exercise and tumor microvessel oxygenation. Citation Format: Jennifer A. Lee, Jennifer M. Wiggins, Lori P. Rice, Dietmar W. Siemann. In vivo fluorescence and spectral microscopy of the effects of aerobic exercise on tumor oxygenation and perfusion in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5211. doi:10.1158/1538-7445.AM2015-5211