Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence-Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model.

Shuya Yano,Robert M Hoffman,Takashi Murakami,Kiyoto Takehara,Shunsuke Kagawa,Toshiyoshi Fujiwara,Yasuo Urata,Michael Bouvet,Shinji Miwa,Yukihiko Hiroshima,Hiroyuki Kishimoto,Shree Ram Singh

doi:10.1371/journal.pone.0148760

Abstract

Fluorescence-guided surgery (FGS) of cancer is an area of intense development. In the present report, we demonstrate that the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 could label colon-cancer liver metastasis in situ in an orthotopic mouse model enabling successful FGS. OBP-401-GFP-labeled liver metastasis resulted in complete resection with FGS, in contrast, conventional bright-light surgery (BLS) did not result in complete resection of the metastasis. OBP-401-FGS reduced the recurrence rate and prolonged over-all survival compared with BLS. In conclusion, adenovirus OBP-401 is a powerful tool to label liver metastasis in situ with GFP which enables its complete resection, not possible with conventional BLS.

Highlights

We demonstrate OBP-401 brightly labels colon cancer liver metastasis in an orthotopic mouse model in situ with green fluorescent protein (GFP), enabling complete resection of liver metastasis by Fluorescence-guided surgery (FGS) and prolonged survival compared to bright-light surgery (BLS)
The tumor margin was invisible in the deep area of the liver under bright light, and RFPexpressing metastatic colon cancer cells remained after BLS (Fig 4A and 4D)
Tumor imaging showed that OBP-401 GFP and the red fluorescent protein (RFP) fluorescence of the metastasis co-localized (Fig 4B)

Summary

Introduction

We demonstrate OBP-401 brightly labels colon cancer liver metastasis in an orthotopic mouse model in situ with GFP, enabling complete resection of liver metastasis by FGS and prolonged survival compared to BLS. FGS was performed under GFP guidance using either a hand-held DinoLite fluorescence imaging system (AM4113T-GFBW Dino-Lite Premier; AnMo Electronics Corp, Taiwan) [14,15] or the stationary Illumatool imaging system (Lightools Research, Encinitas, CA) [16] which enabled precise location of the liver metastasis and surgical-resection beyond the tumor margin. Results and Discussion GFP-Expressing Adenovirus OBP-401 Labels Human Colon Cancer Cells In Vitro

Results

Conclusion