Fluorescence-Guided Surgery

Abstract

Surgical resection of cancer remains an important treatment modality. Despite advances in preoperative imaging, surgery itself is primarily guided by the surgeon's ability to locate pathology with conventional white light imaging. Fluorescence-guided surgery (FGS) can be used to define tumor location and margins during the procedure. Intraoperative visualization of tumors may not only allow more complete resections but also improve safety by avoiding unnecessary damage to normal tissue which can also reduce operative time and decrease the need for second-look surgeries. A number of new FGS imaging probes have recently been developed, complementing a small but useful number of existing probes. In this review, we describe current and new fluorescent probes that may assist FGS.

Keywords: activatable probe; always-on probe; fluorescence-guided surgery; molecular imaging; monoclonal antibodies.

Figure 1

Comparison of molecularly targeted fluorescent probes using always-on and activatable fluorescence strategies. Radiolabeled trastuzumab targeting HER2 with always-on fluorophores depicts both bound and unbound agents (left and right tumors) resulting in poor target-to-background ratio (TBR). In contrast, the activatable fluorescent probe, indocyanine green (ICG)-labeled trastuzumab, depicts only HER2-expressing tumors (right tumor) without incurring background signal resulting in superior TBR. Reprinted from publication (210) with permission from Elsevier.

Figure 2

A schematic explanation of the two types of activatable fluorescence probes. The fluorescence activation of molecularly targeted activatable probes occurs intracellularly (left), whereas enzyme reactive activation typically occurs in the extracellular environment (right). Reprinted with permission from Ref. (203). Copyright 2011 American Chemical Society.

Figure 3

In vivo tumor detection with targeted activatable fluorescent probes in a HER2-positive lung metastasis model mice. The pH-activatable fluorescent probe produces light only in tumors in the lung. However, the control “always-on” probe produces fluorescent signal from both tumors and normal lung and heart reducing the tumor to background ratio. Reprinted with permission from Ref. (155). Copyright 2010 American Chemical Society.

Figure 4

Spectral fluorescence images of four peritoneal ovarian cancers using gGlu-HMRG. In vivo fluorescence intensity of a sprayable probe. By 10 and 60 min after intraperitoneal gGlu-HMRG administration each of four peritoneal ovarian tumor models: SHIN3, OVCAR4, OVCAR5, and OVCAR8 were evaluated. Yellow arrowheads indicate tumor location. Scale bar, 1 cm. Reprinted from publication (112) with permission from AAAS.