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
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Yukie Yoshii1, Mitsuyoshi Yoshimoto2, Hiroki Matsumoto3, Hideaki Tashima1, Yuma Iwao1, Hiroyuki Takuwa1, Eiji Yoshida1, Hidekatsu Wakizaka1, Taiga Yamaya1, Ming-Rong Zhang1, Aya Sugyo1, Sayaka Hanadate1, Atsushi B. Tsuji1 and Tatsuya Higashi1
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
2Division of Functional Imaging, National Cancer Center Hospital East, Chiba, Japan
3Research Center, Nihon Medi-Physics Co., Ltd., Chiba, Japan
Yukie Yoshii, email: [email protected]
Keywords: integrated 64Cu therapy; PET-guided surgery; OpenPET; 64Cu-intraperitoneal radioimmunotherapy; 64Cu-labeled cetuximab
Received: April 04, 2018 Accepted: June 03, 2018 Published: June 22, 2018
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 64Cu-intraperitoneal radioimmunotherapy (ipRIT), alone or in combination with positron emission tomography (PET)-guided surgery using a theranostic agent (64Cu-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. 64Cu-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 64Cu-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 64Cu therapy can serve as a novel treatment strategy for peritoneal dissemination.
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