Page 148 - Fluorescence-guided cancer surgery

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Chapter 9
All the above-mentioned limitations could be overcome by conjugating the folate analog to a uorophore that uoresces in the NIR spectrum. This allows identi cation of structures located deeper beneath the surface due to a lower absorption coe cient, and causes less auto uorescence of normal tissue47. For surface detection of malignant cells, as in breast cancer, depth penetrating is less important, but currently the auto uorescent signal prevented clinical decision-making. Figure S1 (online available) shows uorescence imaging at 500nm and 800nm of breast tissue containing a tumor. These tissue specimens, from patients that were not treated with an exogenous contrast agent as EC17, are thus suitable to demonstrate background auto uorescence. At 500nm high background auto uorescence is observed, while at 800nm no background auto uorescence signal is seen (Supplementary Methods, online available). This illustrates the need for tumor-speci c contrast agents in the NIR spectrum. Currently, our research group is performing a rst-in-human clinical trial in ovarian cancer patients using the FRα speci c near-infrared contrast agent OTL38. Preclinical tests comparing OTL38 with EC17 have demonstrated superiority of OTL38 in sensitivity and brightness48.
In conclusion, administration of EC17 was reasonably well-tolerated and produced clear uorescent signals in ovarian and breast cancer tissue. This allowed resection of 16% more ovarian cancer lesions. Notwithstanding, auto uorescence of benign, predominantly collagen-containing tissues led to detection of a signi cant proportion of false positive lesions in ovarian cancer. Further, auto uorescence resulted in di culty in discriminating breast cancer tissue speci c uorescence from background uorescence. We conclude that FRα is a favorable tumor-speci c target, but EC17 lacks the full set of requirements for uorescence-guided surgery in FRα-positive ovarian and breast cancer, especially because of auto uorescence and insu cient penetration depth. Replacing the 500nm uorophore by a uorophore in the NIR spectrum could likely further improve optical properties and thereby clinical relevance of uorescence-guided surgery.