Program Information
Potential Role of the Glycolytic Oscillator in Acute Hypoxia in Tumors
L Che Fru1*, E Adamson2 , D Campos3 , S Fain4 , S Jacques5 , A van der Kogel6 , K Nickel7 , C Song8 , R Kimple9 , M Kissick10 , (1) University of Wisconsin, Madison, Madison, WI, (2) University of Wisconsin Madison, Madsion, WI, (3) University of Wisconsin Madison, Madison, WI, (4) University of Wisconsin, Madison, WI, (5) Oregon Health and Science University, Portland OR USA, Portland, OR, (6) University of Wisconsin - Madison, Madison, WI, (7) University of Wisconsin Madison, Madison, Wisconsin, (8) University of Wisconsin Madison, Madsion, WI, (9) University of Wisconsin Madison, Madison, WI, (10) University of Wisconsin, Madison, WI
Presentations
WE-FG-BRA-8 (Wednesday, August 3, 2016) 1:45 PM - 3:45 PM Room: Ballroom A
Purpose: Oscillatory dynamics in acute hypoxia have been observed, but poorly understood. They have mostly been attributed to vascular perturbations, but no link has yet been made to metabolic causes. We set out to determine the fundamental frequencies and test for coherence in tumor oxygen dynamics and spatial properties.
Methods: Severe combined immunodeficient (SCID) mice were inoculated onto bilateral flanks with human derived head and neck carcinoma (UW-SCC22) cell line xenografts. Oxygen dynamics were monitored in the tumor every minute for an hour using three modalities: blood oxygen level dependent - magnetic resonance imaging (BOLD-MRI), hemoglobin oxygen saturation photoacoustic, and locally manufactured optical probes for spectral fitting. A statistical test was used to separate fluctuating from non-fluctuating voxels and pixels in BOLD-MRI and photoacoustic data respectively. The power spectrum density (PSD) and the autocorrelation functions were calculated for the time series of each voxel, pixel and region, of the BOLD-MRI, photoacoustic or fiber optic data respectively.
Results: Using all three techniques, intermittent oxygen dynamics with both coherent and incoherent signatures was observed in the tumors. Upon averaging the PSDs of fluctuating voxels and pixels, it was found that these oscillations occurred with periods of minutes to tens of minutes from all three approaches. Observations from the BOLD-MRI and photoacoustic data showed that clusters of voxels oscillated in a synchronized manner.
Conclusion: We were able to use three different modalities to show that fluctuation in tumor oxygen is both coherent and incoherent, with periods of minutes to tens of minutes. These periods are very similar to those from the well-established metabolic, non-linear biomechanical phenomenon called the glycolytic oscillator. This may provide an additional explanation to the cause of cyclic hypoxia. Such dynamics could have profound implications in hypofractionated radiotherapy regiments and could help guide treatment and make it more patient specific.
Funding Support, Disclosures, and Conflict of Interest: The authors would like to thank the University of Wisconsin Carbone Cancer Center (UWCCC) for the funds to complete this project. This work is also supported in part by NIH/NCI P30 CA014520- UW Comprehensive Cancer Center Support".
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