title: 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?
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.
authors.affiliation: Division of Radiology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-n.hayashi@kochi-u.ac.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Hyogo Prefectural Kakogawa Medical Center, Kakogawa, Hyogo 675-8555, Japan. ogaway@kochi-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Diagnostic Radiology &amp; Radiation Oncology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. kubotak@kochi-u.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Division of Radiology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-okinok@kochi-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Okino
authors.affiliation: Division of Radiology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-akima.r@kochi-u.ac.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Akima
authors.affiliation: Division of Radiology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-tokuhiros@kochi-u.ac.jp.
authors.forename: Shiho
authors.initials: S
authors.lastname: Morita-Tokuhiro
authors.affiliation: Division of Radiology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-tsuzukia@kochi-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuzuki
authors.affiliation: Division of Radiology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-yaogawa@kochi-u.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Yaogawa
authors.affiliation: Department of Diagnostic Radiology &amp; Radiation Oncology, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. nishiokaa@kochi-u.ac.jp.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nishioka
authors.affiliation: Department of Pharmacy, Medical School Hospital, Kochi University, Nankoku, Kochi 783-8505, Japan. miyamus@kochi-u.ac.jp.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Miyamura
keywords: KORTUC; hydrogen peroxide; radiation therapy; radiosensitizer; radiotherapy; sodium hyaluronate; tumor hypoxia