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Estimating Tumor Aggressiveness in Head and Neck Cancer Using a Novel Cerenkov Emission Multispectral Optical Probe Based On Silicon Photomultipliers

I Oraiqat1*, A Calcaterra1 , E Al-Snayyan1 , S DeBruin2 , R Clarke1 , A Rehemtulla1 , I El Naqa1 , (1) University of Michigan, Ann Arbor, MI (2) Endectra, LLC, Ann Arbor, MI


(Tuesday, 7/16/2019) 7:30 AM - 9:30 AM

Room: 225BCD

Purpose: Tumor pH has been suggested as an indicator of cancer’s aggressiveness. In this work, we explore the use of a novel Cerenkov emission (CE) multispectral optical probe based on silicon photomultipliers (SiPM) for interrogating tumor aggressiveness and monitoring cancer cell proliferation after various treatment pathways in head and neck cancer.

Methods: Treatment responsive UMSCC47 (HPV+) and resistive UMSCC38 (HPV-) head and neck cancer cells were grown and treated in T25 cell culture flasks in a media containing phenol red (PR) as a pH contrast agent which are placed into a 6MV photon field. Spectral components of the resulting CE are analyzed using a 4-pixel, SiPM-based multispectral optical probe to obtain intensity measurements at 450nm and 560nm, pH is obtained by taking the ratio of these spectral intensities (450nm/560nm) and converting them into a pH reading using a standardized calibration curve, which was prepared from a collection of buffered solutions with PR added at various pH values (6.5 to 7.8). The measured pH is used for quantification of tumor behavior.

Results: The CE multispectral probe pH values measured tracked changes between different treatment pathways as expected for the measured cell survival fractions. As cell populations decreased from treatment, the relative pH with respect to untreated flasks increased (meaning the media becoming less acidic) since there are less cells undergoing metabolic activity. Relative treatment resistance was also identified between the HPV+ cell line and the HPV- cell line with the HPV- cell line demonstrating resistance to treatment as identified by less pH change with respect to the control flask.

Conclusion: This work shows the potential for using SiPM-based probes for CE spectroscopic interrogation for real-time pH measurements during radiotherapy. It was successfully demonstrated in-vitro that these probes can be used to monitor cell proliferation post-therapeutic intervention via estimation of tumor pH.

Funding Support, Disclosures, and Conflict of Interest: This work has been partly sponsored by Endectra, LLC (NSF SBIR Phase II #1632467) and NIH R37CA222215


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