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.
摘要:
对于骨肉瘤(OS)的治疗,必须完全切除所有具有较宽手术切缘的肿瘤组织。然而,这很难,有时是不可能的,实现由于看不见的小卫星病灶和模糊的肿瘤边界。此外,术中冰冻切片分析OS的切除边缘通常受到OS周围硬组织的限制,这使得不可能知道是否实现了负利润率。任何未切除的小肿瘤残留都会导致局部复发和预后恶化。在这里,基于B7H3在OS中的高表达,通过缀合抗B7H3抗体和IRDye800CW来合成靶向探针B7H3-IRDye800CW。B7H3-IRDye800CW可以在静脉给药后准确标记OS区域,从而帮助外科医生识别和切除残余OS病灶(<2mm)和肺转移病灶。在第3天肿瘤背景比达到4.42±1.77。用B7H3-IRDye800CW孵育新鲜的人OS样本后,它可以特异性标记OS区域甚至微侵袭区域(通过苏木精-伊红[HE]染色证实)。探针标记区域与磁共振成像和标本完全HE染色显示的肿瘤区域一致。总之,B7H3-IRDye800CW在术中切除指导和OS的快速病理诊断中具有转化潜力。