title: Development of a Novel Enzyme-Targeting Radiosensitizer (New KORTUC) Using a Gelatin-Based Hydrogel Instead of a Sodium Hyaluronate.
abstract: We recently developed Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC) as a strategy to increase intratumoral oxygen concentrations and degrade antioxidant enzymes such as peroxidase and catalase. We then developed KORTUC II, which uses sodium hyaluronate containing hydrogen peroxide as a radiosensitizer. KORTUC II requires twice-weekly administration to sustain its effects, but decreasing the frequency of radiosensitizer injections to once-weekly would reduce the burden on the patients and the physicians. The goal of this study was thus to develop a new formulation of KORTUC (New KORTUC) that only requires once-weekly administration. We performed experimental studies using a mouse tumor model and biodegradable hydrogel. C3H/He mice were allocated to control, KORTUC, or hydrogel groups. At 72 h after injection, each tumor was irradiated with a 6 MeV electron beam to a total dose of 30 Gy. During a 62-day observation period, changes in tumor volume and survival rates were assessed in each group. Tumor growth rate was slowest in the hydrogel groups. These data suggest that hydrogel could represent a useful adjunct as a long-acting radiosensitizer in place of sodium hyaluronate. New KORTUC, which contains hydrogen peroxide and hydrogel, exerted a radiosensitizing effect that persisted beyond 72 h following injection of the agent. Use of this new formulation allows radiosensitizer injections to be performed once-weekly with good effect.
authors.affiliation: Department of Diagnostic Radiology &amp; Radiation Oncology, Medical school, 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: 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: Division of Radiology, Kochi Medical School Hospital, Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-yokotan@kochi-u.ac.jp.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yokota
authors.affiliation: Division of Radiology, Kochi Medical School Hospital, Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-tsuzukia@kochi-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuzuki
authors.affiliation: Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-oda@kochi-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Oda
authors.affiliation: Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-ishidan@kochi-u.ac.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Ishida
authors.affiliation: Department of Diagnostic Radiology &amp; Radiation Oncology, Medical school, Kochi University, Nankoku, Kochi 783-8505, Japan. jm-aoyama_nobutaka@kochi-u.ac.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Aoyama
authors.affiliation: Department of Diagnostic Radiology &amp; Radiation Oncology, Medical school, Kochi University, Nankoku, Kochi 783-8505, Japan. nishiokaa@kochi-u.ac.jp.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nishioka
keywords: KORTUC; hydrogel; hydrogen peroxide; radiosensitizer; sodium hyaluronate