Major finding: Fluorescently labeled folate can identify tumor masses <1 mm during surgery.
Concept: The vast majority of epithelial ovarian cancers overexpress folate receptor-α (FR-α).
Impact: Real-time imaging with cancer-specific agents can improve tumor staging and excision.
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and is often not diagnosed until advanced stages. Because the most effective treatment for this cancer remains cytoreductive surgery followed by chemotherapy, improved tumor detection would aid debulking efforts and potentially prolong survival. Recent studies have suggested that folate receptor-α (FR-α) is specifically overexpressed in EOC compared to healthy ovarian tissue and is therefore a potentially useful target for imaging. van Dam and colleagues hypothesized that this characteristic of EOC could be exploited through the use of systemically administered fluorescin isothiocyanate (FITC)–conjugated folate, which binds FR-α and is internalized into ovarian cancer cells. In a proof-of-principle study of 10 ovarian tumors, they demonstrate that folate-FITC–labeled tumor cells can be distinguished from surrounding normal tissue with a multispectral fluorescence camera during surgery. Real-time fluorescent labeling enabled surgeons to detect a significantly higher number of tumor masses—some smaller than 1 mm—than visual inspection alone. Histopathology confirmed that the fluorescence was restricted to malignant, FR-α–positive tissues. Furthermore, intravenously injected folate-FITC was safely administered, and the tumor-specific signal persisted up to 8 hours after injection to allow tumor detection during long surgical procedures. However, this approach would not be applicable to the 5% to 10% of EOC cases that do not overexpress FR-α. FR-α is also not uniformly overexpressed in other solid tumors, although preoperative tests may be performed to identify candidates for intraoperative folate imaging. More clinical studies are required to determine if this procedure impacts survival of women with malignant, FR-α–positive EOC, but the improvement of tumor detection to submillimeter size will facilitate tumor cytoreduction and allow more accurate staging of cancers.
van Dam GM, Themelis G, Crane LM, Harlaar NJ, Pleijhuis RG, Kelder W, et al. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med. 2011 Sept 18. [Epub ahead of print]
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