SignificanceThis third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery.AimNational and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed.ApproachPrincipal investigators presenting at the Perelman School of Medicine Abramson Cancer Center’s third clinical trials update on IMI were selected to discuss their clinical trials and endpoints.ResultsDyes that are FDA-approved or currently under clinical investigation in phase 1, 2, and 3 trials were discussed. Sections on how to move benchwork research to the bedside were also included. There was also a dedicated section for pediatric dyes and nonfluorescence-based dyes that have been newly developed.ConclusionsIMI is a valuable adjunct in precision cancer surgery and has broad applications in multiple subspecialties. It has been reliably used to alter the surgical course of patients and in clinical decision making. There remain gaps in the utilization of IMI in certain subspecialties and potential for developing newer and improved dyes and imaging techniques.
The fluorescent imaging agent IS-001 was determined to be well tolerated in all subjects and has the potential to provide ureter visualization throughout minimally invasive hysterectomy procedures. This study was conducted to evaluate clinical safety and efficacy of a real-time ureter visualization technique for use during hysterectomy surgery. The study drug appears safe, is renally excreted, and allows enhanced ureter visualization when imaged with a clinically approved near-infrared sensitive endoscope. This is a first-in-human study showing preliminary results that the drug is safe and effective during surgery for improved ureter visualization.
The purpose of our study is to evaluate patient safety parameters, pharmacokinetics, and ureteral fluorescence/ease of visualization of the compound IS-001, an intravenously administered, renally cleared indigo-cyanine dye in patients undergoing robotic total laparoscopic hysterectomy using the da Vinci Xi Firefly® fluorescent imaging system. Our study design is a Phase I Open Label Case Series Trial. Our intervention is the IV administration of increasing doses (10 mg, 20mg and 40mg) of IS-001 (2mg/mL) in each eight patient cohort. Pharmacokinetic data was collected at predefined intraoperative set points and at 2, 4, and 6 hours post-op to determine maximum blood concentration, total drug exposure, and time course of excretion. Subjective surgeon assessment of ureteral fluorescence was compared to computer calculations of fluorescence intensity to evaluate ease and duration of ureteral visualization using Firefly®. IS-001 appears safe in human subjects. Pharmacokinetic data is consistent with preclinical findings in animal subjects. Subjective surgeon assessment of ureteral fluorescence indicates rapid onset of ureteral fluorescence that persists to a clinically useful degree for 30+ minutes.
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