Page 16 - Fluorescence-guided cancer surgery

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Chapter 1
For several indications, these mechanisms may be su cient for tumor imaging33;35-38. However, there are many more indications that require tailor-made tumor-speci c uorescent ligands. These ligands can either be monoclonal antibodies, antibody fragments, such as single-chain (scFv) or fab fragments, small peptides or structure-inherent targeting uorophores39-42. If these ligands target proteins that are only present on cancer cells, and not on healthy tissue, they could facilitate optimal contrast ratios during imaging. Hanahan and Weinberg elaborated on these hallmarks of cancer, comprising of biological capabilities acquired during the multistep development of human tumors43. Over the past years multiple tumor-speci c agents targeting these hallmarks are developed and validated in various animal models. However, only a few compounds have currently been introduced in clinical studies44-48. This underlines the di culty of bringing tumor-speci c contrast agents to the clinic.
In conclusion, the objective of this thesis is to explore surgical indications where clinically available contrast agents can be used to improve tumor imaging and cancer surgery. Besides, newly developed tumor-speci c contrast agents will be investigated in patients and healthy subjects, to assess their tolerability, pharmacokinetics and pharmacodynamics, and to determine their ability to visualize tumor tissue.
THESIS OUTLINE
This thesis is divided in two parts; Part 1 focuses on the exploration of clinically available NIR uorescent contrast agents for tumor imaging. Part 2 describes the rst in human introduction of newly developed tumor-speci c uorescence contrast agents in both healthy subjects and subsequently patients.
Chapter 2 describes the intraoperative use of indocyanine green (ICG) absorbed to nanocolloid for the detection of sentinel lymph nodes in gastric cancer. Chapter 3 describes the successful detection of breast cancer tissue using methylene blue (MB) at di erent time points. Chapter 4 shows the identi cation of hepatic uveal melanoma metastases during laparoscopic liver surgery using ICG. Chapter 5 demonstrates the intraoperative distinction between normal pituitary gland and pituitary adenoma based on di erences in vascular perfusion patterns during endoscopic transsphenoidal surgery