The Feasibility of Measuring In Vivo Tumor Microenvironment PH During Radiotherapy Using a Novel Cerenkov Emission Multispectral Optical Probe Based On Silicon Photomultipliers
I Oraiqat1*, M Koniczek2,4, R Clarke3,4, A Rehemtulla2, I El Naqa1, (1) H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, (2) University of Michigan - Radiation Oncology, Ann Arbor, MI, (3) University of Michigan - Physics Department, Ann Arbor, (4) Endectra, LLC, Ann Arbor
Presentations
TH-C-TRACK 6-5 (Thursday, 7/29/2021) 1:00 PM - 2:00 PM [Eastern Time (GMT-4)]
Purpose: Tumor pH has been suggested as an indicator of cancer aggressiveness. In this work, we explore the use of a novel Cerenkov Emission (CE) multispectral optical probe based on silicon photomultipliers (SiPM), known as CMSI, for interrogating tumor microenvironment pH in head and neck cancer tumors in a proof-of-principle in vivo demonstration consisting of two mice.
Methods: One mouse was implanted, subcutaneously, on the flank, with the UMSCC47 cell line while the other with an artificial tumor consisting of Matrigel (buffered at a pH of 7.4). During CMSI measurements, the mice were injected with a pH contrast agent consisting of phenol red (PR) and irradiated with 9MV photons. The intensity of CE spectral components at 445nm and 560nm were measured using CMSI and a quantitative value for pH was obtained by taking the ratio of these value (known as the CMSI ratio) in conjunction with a calibration curve, which was prepared from a collection of buffered solutions with PR added at varying pH values (6.5 to 7.8). Calibration was further refined to take into account changes in the CMSI ratio through the mouse tissue by using the artificial tumor pH as a baseline (7.4).
Results: The CMSI ratio measured for the UMSCC47 tumor on the mouse flank is 1.15 compared to the 1.66 measured on the mouse with the benign artificial tumor. By using the pH calibration curve, the corresponding pH value of the UMSCC47 tumor is 6.5 (compared to the baseline of 7.4 in the artificial tumor), showing the cancerous tumor having a more acidic microenvironment.
Conclusion: This work shows the feasibility of using CMSI for CE spectroscopic interrogation for real-time in vivo pH measurements during radiotherapy by successfully demonstrating tumor pH measurements during a pilot mouse study.
Funding Support, Disclosures, and Conflict of Interest: This work is partly supported through NIH phase I STTR (R41CA243722) with Endectra, LLC.
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