Page 137 - Fluorescence-guided cancer surgery

Imaging FRα positive ovarian and breast cancer 135
INTRODUCTION
Over the past decades multiple imaging modalities have become available for preoperative detection of tumors, staging disease and identifying sentinel lymph nodes1;2. However, translation of preoperative obtained images to the surgical theatre can be challenging. Consequently, surgeons largely have to rely on visual inspection and palpation to discriminate between healthy and malignant tissue. As a result, incomplete resection of malignant tissue may occur. In breast cancer surgery, for example, positive resection margins are reported in up to 20% of patients after resection of the primary tumor3. In metastasized disease, intraoperative imaging of tumor tissue can be of great advantage. In ovarian cancer for example, clear intraoperative detection of metastatic lesions can improve staging procedures in early stage ovarian cancer (FIGO I and IIa), and facilitate complete or optimal cytoreductive surgery in advanced stage disease (FIGO IIb to IV). Both the prevention of positive margins in solid tumors and the performance of adequate staging and complete/optimal cytoreduction will improve individual patient outcome4-9. Hence there is a clear unmet need for intraoperative modalities that can identify tumor tissue with high sensitivity and speci city.
An innovative intraoperative optical imaging technique is uorescence imaging. Over the past years multiple studies have been performed on tumor imaging, sentinel lymph node (SLN) mapping and identi cation of vital structures, using uorescence imaging10;11.
Optical properties of uorescent contrast agents are of importance for successful tumor imaging. The wavelength of the uorescent light largely determines the degree of penetration of photons into the tissue. Photons in the visible light range have a depth penetration limited to a few millimeters and are suitable for detection of super cial targets. Conversely photons in the NIR range (650-900 nm) can travel more than a centimeter through tissue, which also enables detection of targets below the tissue surface12. Moreover, the wavelength of the uorescent light also plays a role in auto uorescence. Auto uorescence is uorescence arising from intrinsic tissue components after excitation with UV, visible, or NIR radiation of suitable wavelength. To detect cancer cells targeted with an optical contrast agent, the signal of the target- speci c uorescence must be signi cantly higher than the auto uorescence. The occurrence of auto uorescence is determined by the tissue type and excitation wavelength13;14.