Page 170 - Fluorescence-guided cancer surgery

168
Chapter 10
adverse events were reported. After reviewing the safety and e cacy data collected using all three doses, 0.0125 mg/kg was chosen as the optimal dose for the expansion cohort (patients 10, 11, and 12). In retrospect, this lower dose was a good choice, as adverse symptoms were minimal and TBR was maximal. Table S3 and Figure S6 summarize the TBR results (online available).
Other adverse events
One patient who received a dose of 0.0125 mg/kg OTL38 developed a case of post-operative hospital-acquired pneumonia and coughing-induced wound dehiscence. These complications were considered unrelated to OTL38 administration. The complete list of all adverse events recorded in the patients is provided in Table S4 (online available). Administration of OTL38 itself did not lead to any obvious changes in laboratory values, ECG, vital signs, or temperature.
Pharmacokinetics
The PK pro le of OTL38 in patient blood was similar to the pro le measured in the healthy volunteers. Speci cally, with each dose, the maximum concentration was achieved at the end of the infusion. After stopping the infusion, plasma concentration decreased with a half-life of 2-3 hours (Figure S4).
Intraoperative near-infrared uorescence imaging
Lesions could be detected clearly after OTL38 administration. The optimal camera exposure time was dependent on OTL38 dose, with lower doses requiring longer exposure times. At higher doses, the longer exposure time led to saturated images; however, in all cases it was possible to use a su ciently brief exposure time in order to obtain real-time images.
Figure 3 shows an example of uorescent lesions that were subsequently con rmed as ovarian cancer metastases on histopathology. A total of 83 uorescent lesions were resected during the surgeries; 62 of these lesions were con rmed as malignant on histopathology (i.e., true positives). Strikingly, 18 (29%) of these true positive lesions were not detected using standard inspection and/or palpation methods. Mean TBR was 4.4 (SD: 1.46, range: 1.7- 9.8), and TBR generally decreased with increasing doses, likely due to increased background signal. TBR was constant throughout the surgical procedure, and uorescence could be detected for at least six hours after infusion. Importantly, using NIR uorescence enabled us to detect malignant lesions up to 8 mm