Measuring Tumor Microenvironment pH During Radiotherapy Using a Novel Cerenkov Emission Multispectral Optical Probe Based on Silicon Photomultipliers

Alnawaz Rehemtulla,Ibrahim Oraiqat,Issam El Naqa,Andrew Calcaterra,Roy Clarke,Essam Al-Snayyan

doi:10.3389/fphy.2021.636001

Alnawaz Rehemtulla, Ibrahim Oraiqat + Show 4 more

Open Access

https://doi.org/10.3389/fphy.2021.636001

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Abstract

Cerenkov Emission (CE) multispectral analysis with silicon photomultiplier (SiPM)-based optical probes is a promising tool for online tumor microenvironment interrogation and targeting during radiotherapy delivery. With the extreme sensitivity of SiPMs, deep tissue multispectral CE measurements can be realized in a clinical setting. In this work, we utilize our Cerenkov Emission Multi-spectral Imaging (CMSI) prototype probe to interrogate the spectral components of the CE signal generated during external beam radiotherapy. Our results demonstrated that CMSI enables effective probing of in vitro quantitative changes in the pH of cell media to monitor cancer cell proliferation after various treatment pathways and differentiate between varying treatment resistance cell lines. In addition, the feasibility of using the CMSI probe in vivo was also successfully demonstrated by measuring tumor pH during a pilot mouse study.

Highlights

Cancer is one of the leading causes of the death in the world, and in 2018, it was the second leading cause of death in the United States [1, 2]
Cancerous tumors are comprised of heterogeneous structures consisting of cancer cells and stroma, which are the non-malignant cells that are present in the tumor microenvironment [3]
The human papilloma virus (HPV) negative cell line (UMSCC38) had a higher relative cell survival when compared to the HPV positive (UMSCC47) cells

Summary

Introduction

Cancer is one of the leading causes of the death in the world, and in 2018, it was the second leading cause of death in the United States [1, 2]. Malignant (cancerous) tumors, have an extracellular pH that is lower (more acidic) than the surrounding normal tissue This is caused by aerobic glycolysis ( known as the Warburg Effect) that typically takes place in tumors, where fermentation (i.e., the anaerobic breakdown of glucose into lactate) is preferred over respiration, even in the presence of oxygen [3, 5, 6]. The combination of such fermentation in conjunction with poor tumor vasculature reduces the tumor extracellular pH. An acidic tumor microenvironment is indicative of metabolically aggressive cancer cells, which develop early within the tumor and eventually

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