Page 15 - Fluorescence-guided cancer surgery

emission light, penetration into tissue can be micrometers in the visible light spectrum (400 – 600nm), up to several millimeters to a centimeter in the near- infrared (NIR) light spectrum (700 – 900nm)11;12.
For intraoperative uorescence imaging, both an imaging system and uorescent contrast agent are needed. Moreover, the combination of imaging device and optical properties of the uorophore is of paramount importance for successful intraoperative imaging. The imaging system contains an excitation light source and a detection device to capture emitted uorescence from the exited uorophores. Several imaging systems, either investigational or commercially available, have been developed over the past years for intraoperative uorescence imaging13. As uorescence imaging is gaining more attention, systems optimized for open surgery14-19 and endoscopic surgery20-23 are available at present.
With respect to uorescent contrast agents, there are only a few that have become clinically available over the past decades. These include uorescein24, methylene blue (MB)25, 5-aminolevulinic acid (5-ALA)26 and indocyanine green27. Although some of these contrast agents possess properties to speci cally accumulate inside or around tumors, they are not ligand- targeted contrast agents. This limits the clinical applicability of these compounds for a broad application.
Tumor imaging
For intraoperative tumor imaging, accumulation of a contrast agent in or around the tumor is essential to di erentiate between tumors and surrounding normal structures. Several mechanisms are described that could facilitate this. Ideally, a contrast agent solely binds cancer speci c proteins, while getting excreted from the rest of the body. Development of this kind of contrast agents is an expensive, time-consuming process and requires speci c knowledge, experience in drug-development and an advanced infrastructure. Therefore, it is important to exploit clinically available contrast agents, such as ICG and MB whenever possible. As these contrast agents are not linked to tumor-targeted ligands, other mechanisms such as the enhanced permeability and retention (EPR) e ect28;29, di erence in vascular pattern30-32, disturbed excretion pro les33 and favorable biodistribution of compounds with comparable biophysical properties34 can be explored.
General introduction and thesis outline 13