Presentation Efficacy of combination use of intraperitoneal radioimmunotherapy and PET-guided surgery with 64Cu-labeled-cetuximab in a mice model of colon cancer peritoneal dissemination

Yoshii, Yukie  ,  Yoshimoto, Mitsuyoshi  ,  Matsumoto, Hiroki  ,  Tashima, Hideaki  ,  Iwao, Yuma  ,  Takuwa, Hiroyuki  ,  Yoshida, Eiji  ,  Wakizaka, Hidekatsu  ,  Yamaya, Taiga  ,  Ming-Rong, Zhang  ,  Sugyo, Aya  ,  Hanadate, Sayaka  ,  Tsuji, Atsushi  ,  Higashi, Tatsuya

Objectives: Peritoneal dissemination is a frequent cause of death in colon cancer and it is particularly hard to improve the survival of patients with late-phase peritoneal dissemination. We have reported that intraperitoneal radioimmunotherapy (ipRIT) using a theranostic agent 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab was effective to treat peritoneal dissemination of small lesions. We have also reported that PET-guided surgery with this agent using OpenPET system, which has open space for conducting surgery while monitoring objects at high resolution in real-time PET, was useful to detect and resect intraperitoneal large tumor masses of unknown position. Based on these findings, we examined efficacy of combination use of ipRIT and PET-guided surgery with 64Cu-labeled cetuximab, to treat late-phase peritoneal dissemination of colon cancer, in a mouse model. Methods: Human colon cancer HCT116 cells stably expressing red fluorescent protein (HCT116-RFP) were intraperitoneally injected into a mouse. Four weeks later, mice with late-phase peritoneal dissemination were randomized into 4 groups (n = 8/group). For combination treatment with ipRIT and OpenPET-guided surgery, a therapeutic dose of 64Cu-labeled-cetuximab (22.2 MBq) was ip injected into mice for ipRIT, and OpenPET-guided surgery was performed at 48 h after administration. For comparison purposes, the ipRIT + sham operation, OpenPET-guided surgery-only, or sham operation-only (control) groups were also prepared. For the ipRIT + sham operation group, 64Cu-labeled-cetuximab (22.2 MBq) was injected in a similar manner and the sham operation consisting of resecting only the tumors observed with the naked eye was conducted without OpenPET observation. For the OpenPET-guided surgery-only group, mice were ip administered an imaging dose of 64Cu-labeled-cetuximab (7.4 MBq), and OpenPET-guided surgery was performed at 24 h after the administration. Results: Combination of ipRIT and OpenPET-guided surgery inhibited tumor growth and extended survival significantly compared to the sham operation-only control (P < 0.05). OpenPET-guided surgery alone and ipRIT with a sham operation slightly extended survival, but the differences were not significant compared to the sham operation-only control. Conclusions: We demonstrated the efficacy of a combination therapy of ipRIT and PET-guided surgery for late-phase peritoneal dissemination of colon cancer using a mouse model. Our data suggested that this method could provide a novel strategy to treat late-phase peritoneal dissemination from colon cancer.
SNMMI 2018 Annual Meeting

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