Improved Debulking of Peritoneal Tumor Implants by Near-Infrared Fluorescent Nanobody Image Guidance in an Experimental Mouse Model

• Published in: Molecular imaging and biology Vol. 20; no. 3; pp. 361 - 367
• Main Authors: Debie, Pieterjan, Vanhoeij, Marian, Poortmans, Natalie, Puttemans, Janik, Gillis, Kris, Devoogdt, Nick, Lahoutte, Tony, Hernot, Sophie
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2018; Springer Nature B.V
• Subjects: Animals; Bioluminescence; Brief Article; Cancer; Cell Line, Tumor; Chemotherapy; Cytoreduction Surgical Procedures; Disease Models, Animal; ErbB-2 protein; Female; Fluorescence; Fluorescent indicators; Gastric cancer; Humans; I.R. radiation; Imaging; Implants, Experimental; Infrared imagery; Infrared imaging; Infrared Rays; Lesions; Medicine; Medicine & Public Health; Mice; Nanobodies; Nodules; Optical Imaging; Ovarian cancer; Peritoneal Neoplasms - diagnostic imaging; Peritoneal Neoplasms - surgery; Peritoneum; Radiology; Single-Domain Antibodies - chemistry; Surgery; Surgical implants; Surgical instruments; Tracers; Tumors; Visualization; Nanobody; Targeted tracer; Intraoperative imaging; Near-infrared fluorescent tracer; Fluorescence-guided surgery; Ovarian cancer
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-017-1134-2

Purpose Debulking followed by combination chemotherapy is currently regarded as the most effective treatment for advanced ovarian cancer. Prognosis depends drastically on the degree of debulking. Accordingly, near-infrared (NIR) fluorescence imaging has been proposed to revolutionize cancer surgery by acting as a sensitive, specific, and real-time tool enabling visualization of cancer lesions. We have previously developed a NIR-labeled nanobody that allows fast, specific, and high-contrast imaging of HER2-positive tumors. In this study, we applied this tracer during fluorescence-guided surgery in a mouse model and investigated the effect on surgical efficiency. Procedures 0.5 × 10 6 SKOV3.IP1-Luc+ cells were inoculated intraperitoneally in athymic mice and were allowed to grow for 30 days. Two nanomoles of IRDye800CW-anti-HER2 nanobody was injected intravenously. After 1h30, mice were killed, randomized in two groups, and subjected to surgery. In the first animal group ( n  = 7), lesions were removed by a conventional surgical protocol, followed by excision of remaining fluorescent tissue using a NIR camera. The second group of mice ( n  = 6) underwent directly fluorescence-guided surgery. Bioluminescence imaging was performed before and after surgery. Resected tissue was categorized as visualized during conventional surgery or not, fluorescent or not, and bioluminescent positive or negative. Results Fluorescence imaging allowed clear visualization of tumor nodules within the abdomen, up to submillimeter-sized lesions. Fluorescence guidance resulted in significantly reduced residual tumor as compared to conventional surgery. Moreover, sensitivity increased from 59.3 to 99.0 %, and the percentage of false positive lesions detected decreased from 19.6 to 7.1 %. Conclusions This study demonstrates the advantage of intraoperative fluorescence imaging using nanobody-based tracers on the efficiency of debulking surgery.