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Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under
Fanwei Zeng1, Changjian Li2, Han Wang1
1Department of Musculoskeletal Tumor & Beijing Key Laboratory of Musculoskeletal Tumor, Peking University People's Hospital, Beijing, 100044, China.
Abstract:
Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.
Insights
A novel B7H3-IRDye800CW probe accurately identifies osteosarcoma (OS) during surgery. This targeted imaging helps surgeons remove residual tumor and improve patient outcomes.
Area of Science:
- Oncology
- Surgical Oncology
- Molecular Imaging
Background:
- Complete tumor removal with wide margins is crucial for osteosarcoma (OS) treatment.
- Achieving negative margins is challenging due to microscopic satellite lesions and indistinct tumor boundaries.
- Intraoperative frozen-section analysis is often hindered by hard tissues, complicating margin assessment.
Purpose of the Study:
- To develop and evaluate a targeted fluorescent probe for intraoperative visualization of osteosarcoma.
- To assess the probe's ability to identify residual OS lesions and metastatic sites.
- To explore the probe's utility in rapid pathological diagnosis of OS.
Main Methods:
- Synthesis of a targeted probe (B7H3-IRDye800CW) by conjugating an anti-B7H3 antibody with IRDye800CW.
- Intravenous administration of the probe in OS models to assess tumor labeling.
- Evaluation of probe performance in fresh human OS specimens, comparing with MRI and HE staining.
Main Results:
- B7H3-IRDye800CW accurately labeled OS areas, including microscopic lesions (<2 mm) and potential lung metastases.
- A significant tumor-to-background ratio (4.42 ± 1.77 at day 3) was achieved.
- Probe labeling in fresh specimens correlated well with tumor extent shown by MRI and HE staining, identifying microinvasion.
Conclusions:
- B7H3-IRDye800CW demonstrates high specificity and sensitivity for osteosarcoma.
- The probe facilitates intraoperative identification of residual and metastatic OS lesions.
- B7H3-IRDye800CW holds significant translational potential for improving OS surgical resection and pathological diagnosis.
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