Page 190 - Fluorescence-guided cancer surgery

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Chapter 11
Administration of the folate analogue OTL38 (half life 2-3 hours; molecular weight 1.4 kDa) showed a high uorescent signal in malignant lesions after only 2-3 hours, which prolonged for at least 6 hours (optimal dose 0.0125 mg/kg). Due to the fast clearance of the agent, low background signals were observed. It seems that these properties are ideal for accurate tumor imaging. Future studies will show which compounds are favorable, and this may even di er for di erent surgical indications.
One would ideally develop one contrast agent that targets almost all solid tumors. It remains however challenging to develop a contrast agent that is highly speci c for cancer tissue, while gets excreted from the rest of the body. Receptor expression pro les in tumors can thereby di er. In ovarian cancer for example, over 90% of patients are positive for the FRα, and almost all patients are likely to bene t from treatment with an FRα speci c contrast agent. In cancers where expression pro les are more divers, other strategies must be applied. Preoperative obtained biopsies could be used to explore the receptor expression pro le of a speci c tumor, introducing personalized medicine for precision surgery. This was for example done for the breast cancer patients in our EC17 study. Besides, cocktails with multiple ligand-binding agents can be administered based on biomarker pro les, or so-called multi-headed tumor- speci c contrast agents can be developed. These are compounds that have multiple ligands bound to one uorophore to enlarge the number of receptors that can be bound. A very important hurdle for the design of these agents is that all changes to such molecules can in uence binding capacity and uorescent properties.
One of the main limitations of uorescence imaging is related to tissue penetration. In the visible light spectrum this is in the order of micrometers, improving to approximately 10 mm in the NIR spectrum. To overcome this limitation, contrast agents that combine uorescence imaging with other diagnostic imaging modalities are being developed (multimodal imaging, combined optical positron emission tomography (PET) or single-photon emission computed tomography (SPECT) agents)7. These types of agents allow pre-operative surgical planning, intraoperative guidance towards deeper located targets and real-time visual discrimination of tumors from healthy tissue. In literature, combinations with photoacoustic imaging, magnetic resonance imaging, PET, SPECT and even triple-modal imaging are described8. However, most of these agents are still in a pre-clinical phase of development.