Purpose: Intraoperative localization and resection of ill‐defined pulmonary ground‐glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near‐infrared molecular imaging with a folate receptor–targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins. Methods: In a human trial, 20 subjects with pulmonary GGOs who were eligible for video‐assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near‐infrared imaging. Results: We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near‐infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited. Conclusions: This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.

中文翻译：

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简要报告：用叶酸受体靶向术中分子成像定位肺磨玻璃混浊

目的：在微创肺切除术中对边界不清的肺磨玻璃影 (GGO) 进行术中定位和切除在技术上具有挑战性。目前促进 GGO 定位的术前技术包括微线圈和钩线放置，两者都有后勤限制，存在安全问题，并且无助于边缘评估。在这项临床试验中，我们探索了一种替代方法，包括使用叶酸受体靶向剂 OTL38 进行近红外分子成像，以改善 GGO 的定位和切除边缘的确认。方法：在一项人体试验中，20 名符合电视辅助胸腔镜手术 (VATS) 切除条件的肺 GGO 受试者在切除前接受了 0.025 mg/kg 的 OTL38。主要目标是 (1) 确定使用 OTL38 是否允许在 VATS 期间安全定位 GGO 和评估边缘，以及 (2) 确定预测近红外成像期间荧光量的患者、放射学和组织病理学变量。结果：我们没有观察到毒性。在 21 个 GGO 中，20 个积累了 OTL38 并在原位或后台评估时显示出荧光。术中，近红外成像定位了 21 个病灶中的 15 个，而单独使用 VATS 定位了 21 个中的 10 个（p = 0.05）。通过改善术中定位 (n = 6) 和识别接近边缘 (n = 3)，增加分子成像影响了 21 名受试者中 9 名的护理。这种方法对于小于 2 cm 的胸膜下病变最有效。对于距胸膜表面深度超过 1.5 cm 的病灶，使用荧光反馈的术中定位是有限的。结论：这种方法为术中定位位于外周的小肺部病变提供了一种安全的替代方法。与替代定位技术相比，使用 OTL38 还可以确认足够的余量。未来的研究将在临床试验中将这种方法与替代定位技术进行比较。