63P Assessment of Sunitinib Therapy Using an Integrated Micro-Ultrasound and Photoacoustic System in Mouse Breast Cancer

Abstract

Functional imaging methods that allow non-invasive and longitudinal assessment of the tumor microenvironment are essential in evaluation of cancer therapies. We have developed a new instrument that combines high sensitivity of photoacoustic (PA) imaging and high spatial resolution of micro-ultrasound (µUS). Using this state-of-the-art system, we assessed changes in the tumor microenvironment following treatment with an anti-angiogenic drug, sunitinib (Pfizer, USA). Human metastatic breast cancer cells (231/LM2-4) were surgically implanted in the mammary fat pads of 4 control and 7 treated female nude SCID mice and were allowed to grow for 10 days prior to initiation of experimental treatment, which consisted of either 4 consecutive daily gavage doses of 120mg/kg sunitinib, or control vehicle. Imaging was performed, using the VevoLAZR (VisualSonics, Canada) integrated µUS/PA system, prior to and following treatment. Tumor volume was quantified with 3D ultrasound imaging using a 40MHz frequency probe. Indices of relative blood volume and perfusion were quantified with non-linear contrast imaging using a 21MHz probe during a 50uL (2x109/mL) intravenous bolus injection of microbubbles (MicroMarker, VisualSonics). Blood oxygen saturation, relative tissue oxygen saturation, and hemoglobin concentration were measured with photoacoustic imaging using an integrated photoacoustic probe with 21MHz ultrasound frequency and tuneable 680-970nm laser optics. Following treatment, we observed significant (p < .05) suppression in tumor growth (-35%) decrease in blood volume (-91%), perfusion (-86%), relative tissue oxygen saturation (-60%), and hemoglobin concentration (-40%) in the sunitinib- relative to control-treated mice. When comparing pre- and post-treatment within the control group, there were increases in tumor volume (+120%), however, interestingly, there were also decreases in perfusion (-52%), blood volume (-22%) and relative tissue oxygen saturation (-31%). This study demonstrates the ability of an integrated PA and µUS imaging system to provide quantitative functional assessment of a preclinical breast cancer model following treatment with sunitinib. DisclosureJ. Sun, A. Heinmiller, T. McGrath, D. Bates, A. Needles and C. Theodoropoulos: VisualSonics employee. S. Foster: VisualSonics consultant. All other authors have declared no conflicts of interest.