Page 189 - Fluorescence-guided cancer surgery

FUTURE PERSPECTIVES
Over the past years several indications are identi ed to use clinical available contrast agents for image-guided surgery. ICG and MB have the potential to improve cancer surgery by identifying more malignant lesions, speed up time of surgery, and avoid iatrogenic injury due to better identi cation of vital structures. Although the number of indications is limited due to the intrinsic characteristics of these contrast agents, uorescence-guided surgery can directly be implemented in daily clinical care in for example liver surgery, SLN imaging and expected di cult bile duct surgeries. Until newly developed ligand-binding, tumor-speci c contrast agents have been developed and introduced in the clinic, tumor identi cation can be improved in for example breast cancer surgery, parathyroid surgery and paraganglioma surgery, as discussed in this thesis.
The introduction of ligand-binding, tumor-speci c contrast agents have opened new possibilities for more accurate intraoperative tumor imaging. As long as appropriate tumor or tissue speci c ligands will be discovered, it will be possible to identify almost any structure a surgeon wants to identify during surgery. As shown in our studies, investigating EC17 and OTL38, both folate analogues coupled to uorescent contrast agents resulted in highly speci c tumor imaging, within 2-3 hours after administration. Moreover, the uorescent signal and TBR remained excellent for up to at least 6 hours.
Contrast agents
To achieve accurate tumor detection, it is important to optimize binding capacity, biodistribution and pharmacokinetics of a contrast agent. Multiple compounds as monoclonal antibodies, antibody fragments, such as single- chain antibody fragments and small peptides are therefore being investigated1-5.
These di erent compounds all have their own pharmacokinetic pro les, and thereby di erent intervals for imaging based on the half-life of the agent. Rosenthal et al.5 reported the imaging of head and neck cancer using cetuximab-IRDye800. Surgery was scheduled 3 days after administration of the compound because of the pharmacokinetic pro le of this monoclonal antibody based contrast agent (half life 24 – 32 hours; molecular weight 150 kDa)6. Moreover, relatively high dosages were needed to achieve su cient TBRs (up to 25% of therapeutic dose; 62,5 mg/m2).
Summary and future perspectives 187