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Efficacy of vorinostat-sensitized intraperitoneal radioimmunotherapy with 64Cu-labeled cetuximab against peritoneal dissemination of gastric cancer in a mouse model
Tomoko Tachibana1, Yukie Yoshii1, Hiroki Matsumoto2, Ming-Rong Zhang1, Kotaro Nagatsu1, Fukiko Hihara1, Chika Igarashi1, Aya Sugyo1, Atsushi B Tsuji1, Tatsuya Higashi1
1 National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
2 Nihon Medi-Physics Co., Ltd., Tokyo, Japan
Correspondence Address:
Yukie Yoshii,
National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage, Chiba 263-8555
Japan
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jcrt.JCRT_124_20
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Background: Gastric cancer is a common cause of cancer-related death worldwide, and peritoneal dissemination is the most frequent metastatic pattern of gastric cancer. However, the treatment of this disease condition remains difficult. It has been demonstrated that intraperitoneal radioimmunotherapy (ipRIT) with 64Cu-labeled cetuximab (anti-epidermal growth factor receptor antibody; 64Cu-cetuximab) is a potential treatment for peritoneal dissemination of gastrointestinal cancer in vivo. Recent preclinical and clinical studies have also shown that a histone deacetylase inhibitor, vorinostat, effectively sensitized gastrointestinal cancer to external radiation.
Aim: In the present study, we examined the efficacy of the combined use of vorinostat, as a radiosensitizer during ipRIT with 64Cu-cetuximab in a peritoneal dissemination mouse model with human gastric cancer NUGC4 cells stably expressing red fluorescent protein.
Methods: The mouse model was treated by ipRIT with 64Cu-cetuximab plus vorinostat, each single treatment, or saline (control). Side effects, including hematological and biochemical parameters, were evaluated in similarly treated, tumor-free mice.
Results: Coadministration of ipRIT with 64Cu-cetuximab + vorinostat significantly prolonged survival compared to control and each single treatment. No significant toxicity signals were observed in all treatment groups.
Conclusions: Our data suggest that vorinostat is a potentially effective radiosensitizer for use during the treatment of peritoneal dissemination of gastric cancer by ipRIT with 64Cu-cetuximab.
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