Abstract
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.
Highlights
Peritoneal dissemination is the most common cause of death in gastrointestinal cancers, and conventional therapy provides limited benefits [1]
We developed an integrated 64Cu therapy as a novel strategy to treat early- and late-phase peritoneal dissemination using 64Cu-integrated therapy using 64Cuintraperitoneal radioimmunotherapy (ipRIT), or in combination with positron emission tomography (PET)-guided surgery using the 64Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody cetuximab
We demonstrated that 64Cu-ipRIT inhibited tumor expansion and prolonged survival during early-phase peritoneal dissemination, which involves small tumors and tumor cells that likely spread in the peritoneal cavity
Summary
Peritoneal dissemination is the most common cause of death in gastrointestinal cancers, and conventional therapy provides limited benefits [1]. While no standard treatments are available for peritoneal dissemination, combining chemotherapy with cytoreductive surgery has been performed in clinical practice to treat this condition. Traditional chemotherapy does not effectively diminish tumor lesions in the peritoneal cavity [2]. It is difficult to detect and remove tumors that are located deeply in the peritoneal cavity by cytoreductive surgery. Tumor masses in the peritoneum change their positions during an operation. These difficulties may translate to small effects on improving survival, for late-phase peritoneal dissemination [3]. A need exists for developing more effective drugs and improving surgical procedures to treat peritoneal dissemination
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