Page 164 - Fluorescence-guided cancer surgery

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Chapter 10
Investigational product
OTL38 (chemical formula: C61H63N9Na4O17S4; molecular weight: 1414.42 Da) consists of a folate analog conjugated to an NIR uorescent dye. OTL38 (>96% purity) was obtained from On Target Laboratories (West Lafayette, IN). The drug was synthesized and manufactured at Aptuit (Harrisonville, MO) in compliance with Good Manufacturing Practices (Figure S2, online available). OTL38 was stored in frozen form at -20°C in vials containing 6 mg OTL38 free acid in 3 ml water. Before administration, the frozen vials were thawed, vortexed, and then diluted with 0.9% NaCl or 5% dextrose for intravenous infusion. OTL38 was diluted in either 20 ml or 220 ml and was infused over 10 or 60 minutes. Placebo consisted of a similar volume of 0.9% NaCl or 5% dextrose.
Intraoperative near-infrared uorescence imaging system
Imaging was performed using the Artemis uorescence imaging system (Quest Medical Imaging, Middenmeer, the Netherlands)24. The system consists of three wavelength-isolated light sources, including a “white” light source and two separate near-infrared light sources. For this study, the camera and light engine where optimized for use with OTL38; speci cally, they were designed to generate 7.5 mW/cm2 at 760-nm light. Color video and uorescence images were acquired simultaneously using separate sensors and were displayed in real time using custom-built optics and software, thereby displaying color video and NIR uorescence images separately. A pseudo-colored (lime green) merged image of the color video and uorescence images was also generated. The intensity of the light source was controlled using the Artemis software. The camera was attached to a freely moveable arm. During surgery, the camera and moveable arm were enclosed in a sterile shield and drape (Medical Technique Inc., Tucson, AZ).
Ethics committee approval
Both studies were performed in accordance with the tenets established by the Helsinki Declaration of 1975 (as amended in Tokyo, Venice, Hong Kong, Somerset West, Edinburgh, Washington, and Seoul), ICH-GCP guidelines, and the laws and regulations of the Netherlands. In addition, both studies were approved by a certi ed medical ethics review board. All subjects provided written informed consent prior to the start of any study-related procedures. The healthy volunteer study and ovarian cancer patient study were registered