Abstract 2786: Color-coded fluorescence-guided surgery in a patient-derived orthotopic xenograft (PDOX) nude mouse model of colon-cancer liver metastasis with ICG and a fluorescent antibody
Authors: Nishino Hiroto , Hollandsworth Hannah M. , Amirfakhri Siamak , Filemoni Filemoni , Yamamoto Jun , Tashiro Yoshihiko , Hoffman Robert M. , Bouvet Michael 
Published: September 2020

Background: Liver surgery is the mainstay curative treatment of liver cancer and metastasis. There are two main procedures for liver surgery. One is anatomic resection which is based on the portal flow and the other is partial resection for securing the surgical margin. Indocyanine green (ICG) fluorescence-guided surgery (FGS) has recently been developed in the field of liver surgery. Preoperative ICG administration provides tumor location for partial resection. Intraoperative ICG administration shows the liver segmentation for anatomic resection. However, it is difficult to distinguish between them, especially in the case that tumor lies close to a fluorescent liver segment in a single color image. Our laboratory previously developed color-coded FGS in an orthotopic mouse model of cancer that improved outcome over single color FGS (1). Our aim is to investigate a color-coded FGS to enhance the boundary between the tumor and the transection plane using ICG in combination with a fluorescent-labeled tumor-specific antibody.

Methods: Anti-CEACAM monoclonal antibody (mAb 6G5j) was conjugated to near-infrared dye LI-COR IR700DX (6G5j-IR700DW). A fresh sample of colon-cancer liver metastasis was initially subcutaneously implanted in nude mice. Grown tumors were harvested and cut into small fragments and implanted into the left lobe of the liver of nude mice under anesthesia. After three weeks, mice were administered 50 μg of 6G5j-IR700DW via tail vein injection 48 hours before surgery. 10 μg of ICG was intravenously injected after isolation and ligation of the left Glissonean pedicle during surgery resulting in labeling of the right lobe of the liver. For intra-vital imaging and the FGS procedure, the Pearl Trilogy Small Animal Fluorescence Imaging system (LI-COR) and FLARE Imaging System (Curadel) were used.

Results: On the 700 nm channel, the tumor had a clear fluorescence signal of 6G5j-IR700DW. On the 800 nm channel, the right lobe in the liver had the clear fluorescence signal of ICG and the left lobe had no fluorescence signal due to ligation of the left Glissonean pedicle. Overlay mode on the FLARE Imaging System (bright light, 700 nm and 800 nm) showed clear differentiation between tumor and segmental boundary on the same image. On the overlay mode, FGS for partial liver resection was performed using the 700 nm fluorescence signal of 6G5j-IR700DW. FGS for anatomic left hepatectomy as non-colored area was also well performed using the 800 nm fluorescence signal of ICG.

Conclusions: This preliminary result shows that the combination of ICG (800 nm) and anti-CEACAM antibody conjugated to 700 nm dye has potential for visualization of transection lines and detection of colon-cancer liver metastases for FGS in a single image.

(1) Yano S, et al. Cancer Gene Ther. 2015;22:344-50.

Citation Format: Hiroto Nishino, Hannah M. Hollandsworth, Siamak Amirfakhri, Filemoni Filemoni, Jun Yamamoto, Yoshihiko Tashiro, Robert M. Hoffman, Michael Bouvet. Color-coded fluorescence-guided surgery in a patient-derived orthotopic xenograft (PDOX) nude mouse model of colon-cancer liver metastasis with ICG and a fluorescent antibody [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2786.