Page 146 - Fluorescence-guided cancer surgery

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Chapter 9
because of a low binding constant and fast excretion of the imaging agent after initial biodistribution. The size of the compound greatly in uences this pro le. Currently monoclonal antibodies, antibody fragments, such as single- chain (scFv) of fab fragments, small peptides or structure-inherent targeting uorophores are used for tumor-speci c imaging32-36. The biodistribution, excretion and binding pro le of EC17 shows several great advantages in imaging. The maximum concentration (Cmax) of EC17 is observed directly after the end of administration and is followed by a rapid excretion from the blood. While uorescence signal of the tumor is observed up to more than 5 hours after administration of the compound. This short terminal half-life in blood, strong tumor speci c signal and low background signal allows tumor imaging from 2 hours post dosing and during a relative long time.
Around 75% of patients with ovarian cancer present with advanced stage of the disease37. Multiple studies have shown that the amount of residual disease is the most important prognostic factor for survival in ovarian cancer patients. As a result of these studies, consensus exists that all attempts should be made to achieve complete cytoreduction i.e. complete removal of all macroscopically visible tumor tissue4;6;8;38;39. In this study, real-time visualization of malignant lesions using uorescence imaging during surgery led to the detection of 16% additional malignant lesions. This may improve cytoreduction and hereby patient outcome. The e ect of the addition of intraoperative uorescence imaging on survival was already shown by Stummer et al. in patients with brain glioma. They demonstrated that uorescence imaging with 5-ala not only leads to more complete resections but also to improved progression free survival5. For ovarian cancer more prospective research is necessary to establish the e ect on overall survival.
When patients present with clinically early stage ovarian cancer, a staging procedure is recommended. During this procedure, biopsies of suspicious lesions are taken, supplemented with “blind” biopsies from prede ned locations. Ultimate goal is to identify metastatic lesions whenever present in order to give adequate treatment i.e. systemic chemotherapy. Visualizing metastatic lesions by uorescence imaging may optimize staging procedures, as less “blind” biopsies have to be taken. This could facilitate discrimination between true early stage ovarian cancer and more advanced stage with occult tumor spread. Especially in minimal-invasive surgery, when tactile information (palpation) of lesions cannot be obtained, uorescence imaging could be of additional value.