A proof-of-concept methodology to validate the in situ visualization of residual disease using cancer-targeted molecular agents in fluorescence-guided surgery.
A proof-of-concept methodology to validate the in situ visualization of residual disease using cancer-targeted molecular agents in fluorescence-guided surgery.
复制标题
一种概念验证方法，用于验证在荧光引导手术中使用癌症靶向分子制剂对残留病灶进行原位可视化。
DOI：
10.1117/12.2546190
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Azhdarinia,Ali
中科院分区：
文献类型：
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作者：
Vargas,ServandoHernandez;Lin,Christie;AghaAmiri,Solmaz;Voss,Julie;Ikoma,Naruhiko;TranCao,HopS;Ghosh,SukhenC;Uselmann,AdamJ;Azhdarinia,Ali
临床需要改善术中肿瘤的可视化导致了荧光引导手术（FGS）的靶向造影剂的发展。这些药物的一个关键特征是它们的高肿瘤特异性，这可以检测到可能被视觉检查遗漏的残留病变。在这里，我们研究了一种有前途的生长抑素受体亚型-2 （SSTR2）靶向荧光剂在使用FGS和术后组织病理学验证的小鼠异种移植物中检测残留疾病的效用。方法：植入SSTR2过表达肿瘤的小鼠（n=2）注射2 nmol双标记生长抑素类似物67Ga-MMC(IR800)-TOC，注射后48 h采用传统白光反射和触电法切除肿瘤。肿瘤行伽玛计数和组织病理学分析。采用宽视场FGS成像平台（OnLume）在具有代表性的手术室环境光下评估残留病变情况。结果：采用常规检查和触诊，切除肿瘤边缘大体阴性；然而，FGS成像在肿瘤腔内发现了额外的残余病变。原位荧光肿瘤的噪声对比比（CNRs）分别为3.0和5.2。肿瘤组织累积量分别为7.72和8.20% ID/g，肌肉组织累积量分别为0.27和0.20% ID/g。荧光像素值与γ计数高度相关（r = 0.95, P < 0.048）。H&E和IHC染色分别证实癌阳性和sstr2过表达。结论：我们的研究结果表明，使用临床相关的荧光成像仪器可以增强对有前途的FGS药物的评估，以原位显示残余疾病
Introduction: The clinical need for improved intraoperative tumor visualization has led to the development of targeted contrast agents for fluorescence-guided surgery (FGS). A key characteristic of these agents is their high tumor specificity, which could enable detection of residual lesions that would likely be missed by visual inspection. Here, we examine the utility of a promising somatostatin receptor subtype-2 (SSTR2)-targeted fluorescent agent for detecting residual disease in mouse xenografts using FGS and post-operative histopathological validation.Methods: Mice (n=2) implanted with SSTR2 overexpressing tumors were injected with 2 nmol of the dual-labeled somatostatin analog,67Ga-MMC(IR800)-TOC, and tumors were resected 48 h post-injection using traditional white light reflectance and palpation. Tumors underwent gamma counting and histopathology analysis. The wide-field FGS imaging platform (OnLume) was used to evaluate residual diseasein situunder ambient light representative of an operating room.Results: The tumor was resected with grossly negative margins using conventional inspection and palpation; however, additionalin situresidual disease was found in the tumor cavity using FGS imaging.In situfluorescent tumor contrast-to-noise ratios (CNRs) were 3.0 and 5.2. Agent accumulation was 7.72 and 8.20 %ID/g in tumors and 0.27 and 0.20 %ID/g in muscle. Fluorescence pixel values and gamma counts were highly correlated (r = 0.95, P < 0.048). H&E and IHC staining confirmed cancer positivity and SSTR2-overexpression, respectively.Conclusion: Our findings demonstrate that the use of clinically relevant fluorescence imaging instrumentation enhances the evaluation of promising FGS agents for in situ visualization of residual disease