fluorescent probes; and in a study based on 26 patients, 98% sensitivity and 84%
accuracy in the expansion cohort were achieved [74]. Other antibody-NIR dye
conjugates such as IRDye 800CW or Alexa Fluor 680 also show good clinical
performance [75]. Therefore, NIR antibody combination is a powerful tool in
diagnosis of tumor cells and metastases with high specificity and availability,
providing useful information for decision-making during clinical surgery.
3 Biological Applications
3.1 Imaging-Guided Surgery
Fluorescence molecular imaging has been developed as an emerging tool for
imaging-guided surgery. For precise intraoperative positioning, a fluorescent
fluorophore coupled with an imaging system will be used to help surgeons to
differentiate normal tissues and malignant tissues. Imaging-guided surgeries have
been used for better treatment for liver metastases [76], cervical cancer [77, 78],
melanoma [79, 80], ovarian cancer [81], and vulvar cancer [77]. After injection of
fluorescent contrast agents, imaging guiding system indirectly activates fluorescent
contrast agents with NIR light, followed by image registration processing, providing
video-rate images. The imaging contrast agents and surgical navigation systems are
two most important components of fluorescence molecular imaging technology.
With respect to contrast agents, indocyanine green is a commonly used
FDA-approved dye. It has been used in sentinel lymph node mapping [82] and
hepatic micrometastases detection [83]. In addition, 5-aminolevulinic acid (5-ALA)
was also orally administered to better detect patients with glioma [84]; Alexa-647
was also used to assess tumor margins and better detect head and neck squamous cell
carcinoma [85]. Also, in order to selectively detect tumor, fluorescent contrast agents
were also conjugated with targeting moieties such as sugars, peptides, or antibodies
[86]. As of surgical navigation systems, there are several surgical navigation systems
existing for clinical studies including SPY, Artemis, Photodynamic Eye, Fluobeam,
SurgOptix, FLARE, and GXMI Navigator. SPY system has been utilized to monitor
skin perfusion using ICG as contrast agent during nipple-sparing mastectomies
[87]. FLARE™ imaging systems were created that use three cameras and collect
signals from two NIR channels. FLARE™ imaging systems are mostly used for
intraoperative SLN mapping and cancer surgeries [88, 89]; Artemis™ can collect
both color images and the fluorescent overlay, providing a powerful tool for nerve
surgery. For more detailed surgical navigation systems, readers are referred to these
comprehensive review papers [90, 91]. For example, compared with the white-light
reflectance imaging, the image of main nerve trunk and small branches in muscle
planes was better visualized under fluorescent imaging with organic probes injected
(see Fig. 5).
42
X. Yang et al.
accuracy in the expansion cohort were achieved [74]. Other antibody-NIR dye
conjugates such as IRDye 800CW or Alexa Fluor 680 also show good clinical
performance [75]. Therefore, NIR antibody combination is a powerful tool in
diagnosis of tumor cells and metastases with high specificity and availability,
providing useful information for decision-making during clinical surgery.
3 Biological Applications
3.1 Imaging-Guided Surgery
Fluorescence molecular imaging has been developed as an emerging tool for
imaging-guided surgery. For precise intraoperative positioning, a fluorescent
fluorophore coupled with an imaging system will be used to help surgeons to
differentiate normal tissues and malignant tissues. Imaging-guided surgeries have
been used for better treatment for liver metastases [76], cervical cancer [77, 78],
melanoma [79, 80], ovarian cancer [81], and vulvar cancer [77]. After injection of
fluorescent contrast agents, imaging guiding system indirectly activates fluorescent
contrast agents with NIR light, followed by image registration processing, providing
video-rate images. The imaging contrast agents and surgical navigation systems are
two most important components of fluorescence molecular imaging technology.
With respect to contrast agents, indocyanine green is a commonly used
FDA-approved dye. It has been used in sentinel lymph node mapping [82] and
hepatic micrometastases detection [83]. In addition, 5-aminolevulinic acid (5-ALA)
was also orally administered to better detect patients with glioma [84]; Alexa-647
was also used to assess tumor margins and better detect head and neck squamous cell
carcinoma [85]. Also, in order to selectively detect tumor, fluorescent contrast agents
were also conjugated with targeting moieties such as sugars, peptides, or antibodies
[86]. As of surgical navigation systems, there are several surgical navigation systems
existing for clinical studies including SPY, Artemis, Photodynamic Eye, Fluobeam,
SurgOptix, FLARE, and GXMI Navigator. SPY system has been utilized to monitor
skin perfusion using ICG as contrast agent during nipple-sparing mastectomies
[87]. FLARE™ imaging systems were created that use three cameras and collect
signals from two NIR channels. FLARE™ imaging systems are mostly used for
intraoperative SLN mapping and cancer surgeries [88, 89]; Artemis™ can collect
both color images and the fluorescent overlay, providing a powerful tool for nerve
surgery. For more detailed surgical navigation systems, readers are referred to these
comprehensive review papers [90, 91]. For example, compared with the white-light
reflectance imaging, the image of main nerve trunk and small branches in muscle
planes was better visualized under fluorescent imaging with organic probes injected
(see Fig. 5).
42
X. Yang et al.