Abstract
Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages. Several clinical studies have indicated that the detection and surgery of small resectable PC (<1 cm) can significantly improve survival; however, imaging diagnosis and accurate resection of small PC remain challenging. Here, we report the feasibility of “immuno-OpenPET” as a novel approach enabling not only early diagnosis but also image-guided surgery, using a small (<1 cm) resectable PC orthotopic xenograft mouse model. For immuno-OpenPET, we utilized our original OpenPET system, which enables high-resolution positron emission tomography (PET) imaging with depth-of-interaction detectors, as well as real-time image-guided surgery, by arranging the detectors to create an open space for surgery and accelerating the image reconstruction process by graphics processing units. For immuno-OpenPET, 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab was intraperitoneally administered into mice. It clearly identified PC tumors ≥3 mm. In contrast, neither OpenPET with intravenous-administered 64Cu-cetuximab nor intraperitoneal/intravenous-administered 18F-FDG (a traditional PET probe) could detect PC in this model. Immuno-OpenPET-guided surgery accurately resected small PC in mice and achieved significantly prolonged survival. This technology could provide a novel diagnostic and therapeutic strategy for small resectable PC to improve patient survival.
Highlights
Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages
We previously demonstrated that OpenPET with intraperitoneal administration of anti-epidermal growth factor receptor (EGFR) antibody cetuximab labeled with 64Cu (β+ decay 0.653 MeV, 17.4%; β− decay, 0.574 MeV, 40%; electron capture, 42.6%) was useful for the diagnosis and guided surgery of gastrointestinal cancer-derived tumors in the mouse peritoneal cavity, and intraperitoneal administration of this probe led to their higher accumulation than intravenous injection[18]
We determined that 2 weeks post-tumor implantation was an appropriate time to establish this mouse model, which uniformly formed small resectable PC tumors
Summary
Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages. The OpenPET arranges the detectors to create a sufficient open space for conducting surgical procedures It adopts a rapid image reconstitution system with graphics processing units, which can www.nature.com/scientificreports provide continual images in real time by updating in cycles of
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