Presentation Feasibility of a PET-guided surgery system with 64Cu-labeled-cetuximab in an orthotopic mouse model of pancreatic cancer

Sakurai, Kohei  ,  Yoshii, Yukie  ,  Tashima, Hideaki  ,  Iwao, Yuma  ,  Oe, Yuko  ,  Igarashi, Mineko  ,  Hanadate, Sayaka  ,  Yoshida, Eiji  ,  Wakizaka, Hidekatsu  ,  Yamaya, Taiga  ,  Yoshimoto, Mitsuyoshi  ,  Matsumoto, Hiroki  ,  Ming-Rong, Zhang  ,  Tsuji, Atsushi  ,  Higashi, Tatsuya

Objectives: Pancreatic cancer has one of the poorest prognosis among all types of cancer. Surgery, followed by chemo- and radio-therapy, is the primary treatment for patients with resectable pancreatic cancer; however, there is a need for better visualization of tumor masses in pancreatic tissue during surgery to determine resection sites and margins to improve the efficacy and quality of life. We have reported a novel approach of a PET-guided surgery with 64Cu-labeled-anti-EGFR antibody (cetuximab) and OpenPET system, which has open space for conducting surgery while monitoring objects at high resolution in real time (SNM 2017). In this study, we examined a feasibility of the OpenPET-guided surgery with 64Cu-labeled-cetuximab to detect and resect pancreatic cancers in an orthotopic mouse model. Methods: Human pancreatic cancer xPA cells stably expressing red fluorescent protein (xPA-RFP) were orthotopically injected into a mouse pancreatic tail (n=10). At 1 week after cell inoculation, 64Cu-labeled-cetuximab (7.4 MBq / mouse) was intraperitoneally administered. At 24 h later, the OpenPET-guided surgery was performed with a small prototype of the OpenPET. The prototype had a spatial resolution of about 2 mm. For the OpenPET real-time imaging, one-pass list-mode DRAMA (dynamic row-action maximum-likelihood algorithm) on graphics processing unit was used for high-speed reconstruction, which enables updating cycle of image less than one second while accumulating list-mode data. The parameters of the OpenPET imaging were as follows: voxel size was 1.5 mm; sensitivity and random corrections were applied; absorption and scatter corrections were not applied. Results: The OpenPET-guided surgery clearly detected tumors in the pancreas in all mice. Tumors of 3-10 mm in diameter could be resected by monitoring during OpenPET surgery with real-time imaging. The tumor uptake of 64Cu-labeled-cetuximab was 15.2±4.9 %ID/g. Measurement time to accumulate sufficient list-mode data to identify the tumors was about 10-30 s. Using this system, we detected and resected tumors that could not be clearly identified without OpenPET. It is worth noting that OpenPET was useful to confirm the presence or absence of residual lesions during an operation. Conclusions: We demonstrated an OpenPET-guided surgery with 64Cu-labeled-cetuximab can detect and remove tumor lesions in an orthotopic mouse model of pancreatic cancer. This method could have a potential to provide a novel strategy of image-guided surgery for pancreatic cancer.
SNMMI 2018 Annual Meeting

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