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The development of fluorescence guided surgery for pancreatic cancer: from bench to clinic.

ABSTRACT: INTRODUCTION:Surgeons face major challenges in achieving curative R0 resection for pancreatic cancers. When the lesion is localized, they must appropriately visualize the tumor, determine appropriate resection margins, and ensure complete tumor clearance. Real-time surgical navigation using fluorescence-guidance has enhanced the ability of surgeons to see the tumor and has the potential to assist in achieving more oncologically complete resections. When there is metastatic disease, fluorescence enhancement can help detect these lesions and prevent unnecessary and futile surgeries. Areas covered: This article reviews different approaches for delivery of a fluorescence signal, their pre-clinical and clinical developments for fluorescence guided surgery, the advantages/challenges of each, and their potential for advancements in the future. Expert commentary: A variety of molecular imaging techniques are available for delivering tumor-specific fluorescence signals. Significant advancements have been made in the past 10 years due to the large body of literature on targeted therapies and this has translated into rapid developments of tumor-specific probes.

SUBMITTER: Lwin TM

PROVIDER: S-EPMC6298876 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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The development of fluorescence guided surgery for pancreatic cancer: from bench to clinic.

Lwin Thinzar M TM Hoffman Robert M RM Bouvet Michael M

Expert review of anticancer therapy 20180528 7

<h4>Introduction</h4>Surgeons face major challenges in achieving curative R0 resection for pancreatic cancers. When the lesion is localized, they must appropriately visualize the tumor, determine appropriate resection margins, and ensure complete tumor clearance. Real-time surgical navigation using fluorescence-guidance has enhanced the ability of surgeons to see the tumor and has the potential to assist in achieving more oncologically complete resections. When there is metastatic disease, fluor ...[more]

PMID: 29768067

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Project description:Objective: Fluorescence dyes are increasingly used in brain tumor surgeries, and thus the development of simulation models is important for teaching neurosurgery trainees how to perform fluorescence-guided operations. We aimed to create a tumor model for fluorescence-guided surgery in high-grade glioma (HGG). Methods: The tumor model was generated by the following steps: creating a tumor gel with a similar consistency to HGG, selecting fluorophores at optimal concentrations with realistic color, mixing the fluorophores with tumor gel, injecting the gel into fresh pig/sheep brain, and testing resection of the tumor model under a fluorescence microscope. The optimal tumor gel was selected among different combinations of agar and gelatin. The fluorophores included fluorescein, indocyanine green (ICG), europium, chlorin e6 (Ce6), and protoporphyrin IX (PpIX). The tumor model was tested by neurosurgeons and neurosurgery trainees, and a survey was used to assess the validity of the model. In addition, the photobleaching phenomenon was studied to evaluate its influence on fluorescence detection. Results: The best tumor gel formula in terms of consistency and tactile response was created using 100 mL water at 100°C, 0.5 g of agar, and 3 g of gelatin mixed thoroughly for 3 min. An additional 1 g of agar was added when the tumor gel cooled to 50°C. The optimal fluorophore concentration ranges were fluorescein 1.9 × 10-4 to 3.8 × 10-4 mg/mL, ICG 4.9 × 10-3 to 9.8 × 10-3 mg/mL, europium 7.0 × 10-2 to 1.4 × 10-1 mg/mL, Ce6 2.2 × 10-3 to 4.4 × 10-3 mg/mL, and PpIX 1.8 × 10-2 to 3.5 × 10-2 mg/mL. No statistical differences among fluorophores were found for face validity, content validity, and fluorophore preference. Europium, ICG, and fluorescein were shown to be relatively stable during photobleaching experiments, while chlorin e6 and PpIX had lower stability. Conclusions: The model can efficiently highlight the "tumor" with 3 different colors-green, yellow, or infrared green with color overlay. These models showed high face and content validity, although there was no significant difference among the models regarding the degree of simulation and training effectiveness. They are useful educational tools for teaching the key concepts of intra-axial tumor resection techniques, such as subpial dissection and nuances of fluorescence-guided surgery.

Project description:The use of cancer-targeted contrast agents in fluorescence-guided surgery (FGS) has the potential to improve intraoperative visualization of tumors and surgical margins. However, evaluation of their translational potential is challenging. We examined the utility of a somatostatin receptor subtype-2 (SSTR2)-targeted fluorescent agent in combination with a benchtop near-infrared fluorescence (NIRF) imaging system to visualize mouse xenografts under conditions that simulate the clinical FGS workflow for open surgical procedures. The dual-labeled somatostatin analog, Ga67-MMC(IR800)-TOC, was injected into mice (n = 24) implanted with SSTR2-expressing tumors and imaged with the customized OnLume NIRF imaging system (Madison, Wisconsin). In vivo and ex vivo imaging were performed under ambient light. The optimal dose (0.2, 0.5, and 2 nmol) and imaging time point (3, 24, 48, and 72 h) were determined using contrast-to-noise ratio (CNR) as the image quality parameter. Video captures of tumor resections were obtained to provide an FGS readout that is representative of clinical utility. Finally, a log-transformed linear regression model was fitted to assess congruence between fluorescence readouts and the underlying drug distribution. The drug-device combination provided high in vivo and ex vivo contrast (CNRs > 3, except lung at 3 h) at all time points with the optimal dose of 2 nmol. The optimal imaging time point was 24-h post-injection, where CNRs > 6.5 were achieved in tissues of interest (i.e., pancreas, small intestine, stomach, and lung). Intraoperative FGS showed excellent utility for examination of the tumor cavity pre- and post-resection. The relationship between fluorescence readouts and gamma counts was linear and strongly correlated (n = 334, R2 = 0.71; r = 0.84; P < 0.0001). The innovative OnLume NIRF imaging system enhanced the evaluation of Ga67-MMC(IR800)-TOC in tumor models. These components comprise a promising drug-device combination for FGS in patients with SSTR2-expressing tumors.

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The development of fluorescence guided surgery for pancreatic cancer: from bench to clinic.

Publications

The development of fluorescence guided surgery for pancreatic cancer: from bench to clinic.

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