Computed Tomography Demonstration of the Production and Distribution of Oxygen Gas Following Intratumoral Injection of a New Radiosensitizer (KORTUC) for Patients with Breast Cancer—Is Intratumoral Injection Not an Ideal Approach to Solve the Major Problem of Tumor Hypoxia in Radiotherapy?

Naoya Hayashi,Akihito Nishioka,Yasuhiro Ogawa,Kazuhiro Okino,Kei Kubota,Ryo Akima,Shiho Morita-Tokuhiro,Shin Yaogawa,Mitsuhiko Miyamura,Akira Tsuzuki

doi:10.3390/cancers8040043

Naoya Hayashi, Akihito Nishioka + Show 8 more

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https://doi.org/10.3390/cancers8040043

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Journal: Cancers	Publication Date: Apr 1, 2016
Citations: 22	License type: CC BY 4.0

Affiliation: Kōchi University, Kochi Medical School Hospital

Abstract

We previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate for injection into various types of tumors. For breast cancer treatment, the radiosensitization agent was injected into the tumor tissue twice a week under ultrasonographic guidance, immediately prior to each administration of radiation therapy. At approximately three hours after the second or third injection, computed tomography (CT) was performed to confirm the production and distribution of oxygen gas generated from the KORTUC radiosensitization agent by catalysis of peroxidases contained mainly in tumor tissue. The purpose of this study was to demonstrate that tumor hypoxia could be overcome by such a procedure and to evaluate the method of intratumoral injection in terms of confirming oxygen distribution in the target tumor tissue and around the tumor to be visualized on dedicated CT imaging. Three-dimensional reconstructed maximum intensity projection imaging of contrast-enhanced breast magnetic resonance imaging was used to compare the position of the tumor and that of the generated oxygen. Distributed oxygen gas was confirmed in the tumor tissue and around it in all 10 patients examined in the study. A region of oxygen gas was measured as an average value of −457.2 Hounsfield units (HU) as a region of interest. A slightly increased HU value compared to the density of air or oxygen was considered due to the presence of tumor tissue in the low-density area on 5-mm-thick reconstructed CT imaging. The results of this study showed that intratumoral oxygen was successfully produced by intratumoral KORTUC injection under ultrasonographic guidance, and that tumor hypoxia, which is considered a main cause of radioresistance in currently used Linac (linear accelerator) radiation therapy for malignant neoplasms, could be resolved by this method.

Highlights

Low linear energy transfer (LET) radiation, such as X-rays and electron beams from a linear accelerator (Linac), is mainly used for clinical radiotherapy worldwide
To confirm oxygen production and evaluate the distribution of oxygen gas, computed tomography (CT) examinations were performed approximately 3 h after the second or third radiosensitization agent injection for 10 patients for whose breast cancer it seemed to be relatively difficult to obtain an even distribution of oxygen gas throughout the target tumor guided by ultrasonographic studies alone
In all 10 patients shown in Table 1, production and distribution of oxygen gas were confirmed in and around the tumor tissue

Summary

Introduction

Low linear energy transfer (LET) radiation, such as X-rays and electron beams from a linear accelerator (Linac), is mainly used for clinical radiotherapy worldwide. We recently developed a new enzyme-targeting radiosensitization treatment, KORTUC (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas) using hydrogen peroxide and sodium hyaluronate for intratumoral injection [3,4,5,6,7,8,9], and the safety and effectiveness of the treatment have been demonstrated mainly for patients with locally-advanced neoplasms [10,11,12,13,14,15,16,17,18,19]. To confirm oxygen production and evaluate the distribution of oxygen gas, CT examinations were performed approximately 3 h after the second or third radiosensitization agent injection for 10 patients for whose breast cancer it seemed to be relatively difficult to obtain an even distribution of oxygen gas throughout the target tumor guided by ultrasonographic studies alone.

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