In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized⁶⁴Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study

Peritoneal dissemination of pancreatic cancer has a poor prognosis. We have reported that intraperitoneal radioimmunotherapy using a⁶⁴Cu-labeled antibody (⁶⁴Cu-ipRIT) is a promising adjuvant therapy option to prevent this complication. To achieve personalized⁶⁴Cu-ipRIT, we developed a new in vitro tumor cell-binding assay (⁶⁴Cu-TuBA) system with a panel containing nine candidate⁶⁴Cu-labeled antibodies targeting seven antigens (EGFR, HER2, HER3, TfR, EpCAM, LAT1, and CD98), which are reportedly overexpressed in patients with pancreatic cancer. We investigated the feasibility of⁶⁴Cu-TuBA to select the highest-binding antibody for individual cancer cell lines and predict the treatment response in vivo for⁶⁴Cu-ipRIT.⁶⁴Cu-TuBA was performed using six human pancreatic cancer cell lines. For three cell lines, an in vivo treatment study was performed with⁶⁴Cu-ipRIT using high-, middle-, or low-binding antibodies in each peritoneal dissemination mouse model. The high-binding antibodies significantly prolonged survival in each mouse model, while low-and middle-binding antibodies were ineffective. There was a correlation between in vitro cell binding and in vivo therapeutic efficacy. Our findings suggest that⁶⁴Cu-TuBA can be used for patient selection to enable personalized⁶⁴Cu-ipRIT. Tumor cells isolated from surgically resected tumor tissues would be suitable for analysis with the⁶⁴Cu-TuBA system in future clinical studies.