Title: Integrated treatment using intraperitoneal radioimmunotherapy and positron emission tomography-guided surgery with 64Cu-labeled cetuximab to treat early- and late-phase peritoneal dissemination in human gastrointestinal cancer xenografts
Abstract: // Yukie Yoshii 1 , Mitsuyoshi Yoshimoto 2 , Hiroki Matsumoto 3 , Hideaki Tashima 1 , Yuma Iwao 1 , Hiroyuki Takuwa 1 , Eiji Yoshida 1 , Hidekatsu Wakizaka 1 , Taiga Yamaya 1 , Ming-Rong Zhang 1 , Aya Sugyo 1 , Sayaka Hanadate 1 , Atsushi B. Tsuji 1 and Tatsuya Higashi 1 1 National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan 2 Division of Functional Imaging, National Cancer Center Hospital East, Chiba, Japan 3 Research Center, Nihon Medi-Physics Co., Ltd., Chiba, Japan Correspondence to: Yukie Yoshii, email: [email protected] Keywords: integrated 64 Cu therapy; PET-guided surgery; OpenPET; 64 Cu-intraperitoneal radioimmunotherapy; 64 Cu-labeled cetuximab Received: April 04, 2018 Accepted: June 03, 2018 Published: June 22, 2018 ABSTRACT Peritoneal dissemination is a common cause of death from gastrointestinal cancers and is difficult to treat using current therapeutic options, particularly late-phase disease. Here, we investigated the feasibility of integrated therapy using 64 Cu-intraperitoneal radioimmunotherapy (ipRIT), alone or in combination with positron emission tomography (PET)-guided surgery using a theranostic agent ( 64 Cu-labeled anti-epidermal growth factor receptor antibody cetuximab) to treat early- and late-phase peritoneal dissemination in mouse models. In this study, we utilized the OpenPET system, which has open space for conducting surgery while monitoring objects at high resolution in real time, as a novel approach to make PET-guided surgery feasible. 64 Cu-ipRIT with cetuximab inhibited tumor growth and prolonged survival with little toxicity in mice with early-phase peritoneal dissemination of small lesions. For late-phase peritoneal dissemination, a combination of 64 Cu-ipRIT for down-staging and subsequent OpenPET-guided surgery for resecting large tumor masses effectively prolonged survival. OpenPET clearly detected tumors (≥3 mm in size) behind other organs in the peritoneal cavity and was useful for confirming the presence or absence of residual tumors during an operation. These findings suggest that integrated 64 Cu therapy can serve as a novel treatment strategy for peritoneal dissemination.