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Researchers developed and tested fluorescence probes that can rapidly detect small peritoneal metastases during surgery for high-grade serous ovarian carcinoma, the most aggressive type of ovarian cancer. By screening 381 fluorescence probes on patient tissue samples, they identified three probes (EK-HMRG, NA-HMRG, and DA-HMRG) that target puromycin-sensitive aminopeptidase (PSA) and can visualize millimeter-sized tumor deposits within minutes of topical application. The probes demonstrated high sensitivity and specificity in both clinical specimens and mouse models of peritoneal dissemination.
Why it matters
Complete surgical removal of all tumor tissue is critical for improving survival in ovarian cancer patients, but surgeons often miss tiny metastatic lesions during conventional visual inspection. These fluorescence probes could enable real-time intraoperative detection of previously invisible tumors, potentially improving complete resection rates and patient outcomes in one of the deadliest gynecologic cancers.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background: Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic malignancies, largely because most patients are diagnosed at an advanced stage with peritoneal dissemination. High-grade serous carcinoma (HGSC), the most common and aggressive EOC subtype, requires complete cytoreductive surgery to improve the prognosis; however, minute disseminated lesions are often missed by conventional intraoperative inspection. Here, we aimed to develop fluorescence probes for rapid and sensitive intraoperative detection of HGSC peritoneal dissemination. Methods: We screened a hydroxymethyl rhodamine green (HMRG)-based fluorescence probe library consisting of 381 protease- and aminopeptidase-reactive fluorescence probes using tumor and non-tumor specimens from patients with HGSC. The target enzyme of the hit probes was identified by means of enzyme assays, immunohistochemistry, and LC/MS analysis. Diagnostic utility was evaluated ex vivo using clinical specimens and in vivo using a peritoneal dissemination mouse model. Results: Three probes–EK-HMRG, NA-HMRG and DA-HMRG–were selected as promising candidates for the detection of peritoneal dissemination in HGSC. Puromycin-sensitive aminopeptidase (PSA) was identified as a novel target enzyme of these probes. EK-HMRG, NA-HMRG and DA-HMRG rapidly detected peritoneal dissemination just a few millimeters in size with high sensitivity and specificity in clinical HGSC specimens and in a peritoneal dissemination mouse model after topical application. Conclusions: The PSA-targeting topical fluorescence probes EK-HMRG, NA-HMRG and DA-HMRG are promising tools for real-time, highly sensitive intraoperative visualization of peritoneal dissemination in HGSC, and are promising candidates to improve complete resection rates.