Comparative Experience of Short-wavelength Versus Long-wavelength Fluorophores for Intraoperative Molecular Imaging of Lung Cancer.
Comparative Experience of Short-wavelength Versus Long-wavelength Fluorophores for Intraoperative Molecular Imaging of Lung Cancer.
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肺癌术中分子成像的短波长与长波长荧光团的比较经验。
DOI：
10.1097/sla.0000000000005596
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发表时间：
2022-10-01
影响因子：
9
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术中分子成像（IMI）使用肿瘤靶向光学造影剂可以改善肿瘤切除。IMI示踪荧光团的最佳波长从未在人体中进行过研究，对该领域具有重大影响。为了解决这个问题，我们研究了2个光谱上不同的荧光基团共轭到相同的靶向配体上。在2011年12月至2021年11月期间，原发性肺癌患者术前输注两种叶酸受体靶向对比示踪剂之一：短波叶酸-荧光素（EC17, λem =520 nm）或长波叶酸- s0456（帕帕拉夏氨酸，λem =793 nm）。在切除过程中，IMI用于识别肺结节和确定边缘。前瞻性地收集人口统计学资料、病变诊断和荧光数据。282例患者接受了叶酸-荧光素（n=71, 25.2%）或帕帕拉津氨酸（n=211, 74.8%）的原发性肺癌切除术。大多数肿瘤（n=208, 73.8%）为浸润性腺癌。我们确定了IMI的两种临床应用：定位不可触及病变（n=39, 13.8%）和检测阳性边缘（n=11, 3.9%）。在每种应用中，长波示踪剂在穿透深度、信本比（SBR）和事件频率方面都优于短波示踪剂。帕福拉津氨酸在检测胸膜下病变方面更有效（叶酸-荧光素的平均SBR为2.71比1.73,p<0.0001）。信号检测限为距胸膜表面1.8 cm，距叶酸荧光素0.3 cm。在人体组织中，长波近红外荧光团优于短波近红外荧光团。因此，未来治疗所有人类癌症的努力应该集中在长波剂上。在这项研究中，我们回顾性地回顾了十年来在术中分子成像（IMI）引导下肺癌切除术的经验。我们的目的是探讨示踪剂荧光团的最佳波长，为指导患者和示踪剂的选择提供临床依据。
Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve cancer resections. The optimal wavelength of the IMI tracer fluorophore has never been studied in humans and has major implications for the field. To address this question, we investigated 2 spectroscopically distinct fluorophores conjugated to the same targeting ligand. Between December 2011 and November 2021, patients with primary lung cancer were preoperatively infused with one of two folate receptor-targeted contrast tracers: a short wavelength folate-fluorescein (EC17; λem =520 nm) or a long wavelength folate-S0456 (pafolacianine; λem =793 nm). During resection, IMI was utilized to identify pulmonary nodules and confirm margins. Demographic data, lesion diagnoses, and fluorescence data were collected prospectively. Two hundred and eighty-two patients underwent resection of primary lung cancers with either folate-fluorescein (n=71, 25.2%) or pafolacianine (n=211, 74.8%). Most tumors (n=208, 73.8%) were invasive adenocarcinomas. We identified two clinical applications of IMI: localization of non-palpable lesions (n=39 lesions, 13.8%) and detection of positive margins (n=11, 3.9%). In each application, the long wavelength tracer was superior to the short wavelength tracer regarding depth of penetration, signal-to-background ratio (SBR), and frequency of event. Pafolacianine was more effective for detecting subpleural lesions (mean SBR 2.71 vs. 1.73 for folate-fluorescein, p<0.0001). Limit of signal detection was 1.8 cm from the pleural surface for pafolacianine and 0.3 cm for folate-fluorescein. Long wavelength NIR fluorophores are superior to short wavelength IMI fluorophores in human tissues. Therefore, future efforts in all human cancers should likely focus on long wavelength agents. In this study, we retrospectively reviewed our decade-long experience with intraoperative molecular imaging (IMI)-guided resection of lung cancer. Our objective was to investigate the optimal wavelength of tracer fluorophore, as well as provide clinical pearls to guide patient and tracer selection.