Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery.

Fortuné M.K Elekonawo,Johannes H.W De Wilt,Desirée L Bos,Andreas J.A Bremers,Mark Rijpkema,David M Goldenberg,Lodewijk A.A Brosens,Jan Marie De Gooyer,Otto C Boerman

doi:10.3390/cancers12040987

Abstract

Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

Highlights

Successful surgical treatment of many cancers relies on complete tumor resection; incomplete resection increases the odds of recurrence [1,2,3,4,5,6,7]
Six patients were diagnosed with a peritoneally metastasized adenocarcinoma, and in three patients the peritoneal metastases originated from a mucinous adenocarcinoma
Together with earlier results on biodistribution and tumor accumulation, these results indicate that it is feasible to use this tracer for fluorescence image-guided surgery in patients with colorectal peritoneal metastases

Summary

Introduction

Successful surgical treatment of many cancers relies on complete tumor resection; incomplete resection increases the odds of recurrence [1,2,3,4,5,6,7]. In late-stage cancers, complete resection of tumors and accurate detection of their metastases remains challenging. Intraoperative imaging techniques, such as real-time near-infrared fluorescence imaging, might help to overcome these challenges [8]. Several clinical trials in patients with various types of cancer are ongoing, and others have demonstrated that fluorescent imaging probes can be used for intraoperative or postoperative evaluation of tumor margins and the presence of cancer [9,10]. Cancers 2020, 12, 987 or multimodal tracers might help to increase the surgeons’ ability to discriminate between healthy and malignant tissue, and several clinical trials in different cancers evaluated their use [8].

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