Page 165 - Fluorescence-guided cancer surgery

Clinical translation of OTL38 in ovarian cancer 163
in the European Clinical Trials Database under numbers 2013-004774-10 and 2014-002352-12, respectively; publicly accessible via the CCMO register (https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm).
Practical evaluation
Directly following the surgical procedure, the surgeon was asked to complete a questionnaire regarding the practical application of the technique during the surgical procedure (Supplementary Materials and Methods, online available).
Visual detection
Color and uorescence images of seven representative surgical views of patients with con rmed ovarian cancer were captured from the videos recorded using the Artemis imaging system. Intra-observer variability was assessed by including a matching color and uorescence image set twice (one set was a horizontal mirror image of the original), resulting in a total of eight sets of matching color and uorescence images that were printed in full color; representative images are shown in Figure 2. Three experienced gynecological oncologists were asked to mark clinically suspected lesions directly on the color images; they were then asked to mark clinically suspected lesions on the matching uorescence images. Visual detection was performed ex vivo because intraoperative assessment of the number of lesions was not feasible.
Pharmacokinetics analysis
The bioanalysis was performed using validated methodologies in compliance with good clinical laboratory practices at Analytical Biochemical Laboratory (Assen, the Netherlands). In brief, OTL38 was extracted from human K2EDTA plasma samples and urine samples using o -line solid-phase extraction, followed by analysis using liquid chromatography-mass spectrometry (APL- 4000, Attodyne Inc., Toronto, Ontario, Canada). The assay’s lower limit of quanti cation (LLOQ) and upper limit of quanti cation (ULOQ) were 2.00 and 500 ng/ml, respectively. The coe cient of variability for intra-day and inter-day plasma LLOQ and urine LLOQ was 8.2% and 13.3%, respectively.