Page 173 - Fluorescence-guided cancer surgery

Clinical translation of OTL38 in ovarian cancer 171
Visual detection
The examination of tumor deposits based on color images obtained from the intraoperative videos allowed us to identify an average of 8.3 (SD: 5.4, range: 1-18) lesions per image. In contrast, performing the same assessment using the matching NIR uorescence images allowed us to identify an average of 17.6 (SD: 10.8, range: 5-45) lesions per image, re ecting a more than two-fold improvement in our ability to detect tumor lesions (Figure 2).
Practical evaluation
The use of uorescence imaging did not interfere with the surgeon’s ability to perform cytoreductive surgery, and the majority of participating surgeons reported that they found the technique to be useful (Supplementary Materials and Methods).
DISCUSSION
Here, we report the successful use of the rst tumor-speci c NIR uorescence- based imaging agent to target FRα in ovarian cancer, signi cantly increasing removal of tumor lesions.
In healthy volunteers, OTL38 caused moderate hypersensitivity; however, these reactions were easily managed. Given their symptomology, these reactions were likely pseudoallergic, a nding that has been described previously by Szebeni with respect to radiocontrast media25. Moreover, investigating the cause of this hypersensitivity led to the development of procedures designed to minimize or eliminate this reaction in our subsequent study with cancer patients. This was likely related to aggregation of OTL38 rather than a classic allergic response to the drug, suggesting that the severity may be reduced further by modifying the drug’s formulation. Regardless, even these reactions were not severe enough to preclude the administration of a single dose of OTL38.
In healthy volunteers, the agent was essentially cleared from the plasma within 2-3 hours of intravenous delivery; however, a stable signal remained visible in the skin for at least six hours after dosing. This information was extremely valuable for determining the optimal time window for intraoperative imaging in patients, in which a favorable TBR was required during the surgical