A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer.
A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer.
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DOI：
10.1007/s00259-021-05372-6
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发表时间：
2021-10
影响因子：
9.1
通讯作者：
Reiner, Thomas
中科院分区：
文献类型：
--
作者：
Demetrio de Souza Franca, Paula;Kossatz, Susanne;Brand, Christian;Karassawa Zanoni, Daniella;Roberts, Sheryl;Guru, Navjot;Adilbay, Dauren;Mauguen, Audrey;Valero Mayor, Cristina;Weber, Wolfgang A.;Schoder, Heiko;Ghossein, Ronald A.;Ganly, Ian;Patel, Snehal G.;Reiner, Thomas
局部应用PARPi-FL是一种分子特异性、基于荧光造影剂的技术，可以满足对口腔癌早期诊断的简单、体内、非侵入性、成本效益高的即时检测方法的未满足需求。我们介绍了局部应用PARPi-FL的I期安全性和可行性研究的结果，以确定PARPi-FL的使用是否安全，并提供适合区分口腔鳞状细胞癌（OSCC）和健康周围边缘组织的对比。12例OSCC患者提供了本临床研究的书面同意书。患者用PARPi-FL溶液（15 mL、100 nM、250 nM、500 nM或1000 nM）漱口60秒，然后用清洁溶液漱口60秒。在PARPi-FL应用之前、PARPi-FL应用之后和清洁之后，对病变和周围口腔粘膜进行荧光测量。在示踪剂给药前后采集患者生命体征和血液样本。PARPi-FL耐受性良好，所有患者均无任何安全性问题。PARPi-FL生成的造影剂可区分病变和周围边缘。在施用PARPi-FL后，所有恶性病变均显示出显著的对比度，其中最高的增加发生在最高剂量水平（1000 nM），其中所有患者的肿瘤与边缘荧光信号比> 3。清除步骤对于增加信号特异性是必不可少的，因为它清除了捕获在正常解剖结构中的未结合的PARPi-FL。PARPi-FL特异性通过离体桌面共聚焦显微镜证实。荧光信号来自肿瘤细胞的细胞核，支持我们在亚细胞水平上的宏观发现。PARPi-FL swish & spit解决方案是一种快速和非侵入性的诊断工具，优先定位OSCC的荧光对比。该技术有望通过对口腔可疑病变进行活体光学评估和靶向活检来早期发现口腔鳞状细胞癌。
Topically applied PARPi-FL is a molecularly specific, fluorescent contrast-based technology that may fulfill the unmet need for a simple, in vivo, non-invasive, cost-effective, point-of-care method for the early diagnosis of oral cancer. We present results from a phase I safety and feasibility study on topically applied PARPi-FL to determine if the use of PARPi-FL is safe and provides contrast suitable for discriminating between squamous cell carcinoma of the oral cavity (OSCC) and healthy surrounding margin tissue. Twelve patients OSCC provided written consent for this clinical study. The patients gargled a PARPi-FL solution for 60 seconds (15 mL, 100 nM, 250 nM, 500 nM, or 1000 nM), followed by gargling a clearing solution for 60 seconds. Fluorescence measurements of the lesion and surrounding oral mucosa were taken before PARPi-FL application, after PARPi-FL application, and after clearing. Patient vitals and blood samples were obtained before and after tracer administration. PARPi-FL was well-tolerated and by all patients without any safety concerns. PARPi-FL generated contrast allowing to discriminate between lesion and surrounding margin. All malignant lesions showed significant contrast after administration of PARPi-FL, with the highest increase occurring at the highest dose level (1000 nM), where all patients had a tumor-to-margin fluorescence signal ratio of > 3. A clearing step was essential to increase signal specificity, as it clears unbound PARPi-FL trapped in normal anatomical structures. PARPi-FL specificity was confirmed by ex vivo tabletop confocal microscopy. The fluorescence signal arose from the nuclei of tumor cells, endorsing our macroscopic findings on a sub-cellular level. A PARPi-FL swish & spit solution is a rapid and non-invasive diagnostic tool that preferentially localizes fluorescent contrast to OSCC. This technique holds promise for the early detection of OSCC based on in vivo optical evaluation and targeted biopsy of suspicious lesions in the oral cavity.
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影响因子：
3.7
作者：
Kossatz S;Weber WA;Reiner T
通讯作者：
Reiner T
影响因子：
6.4
作者：
Kaur, Jatinder;Matta, Ajay;Ralhan, Ranju
通讯作者：
Ralhan, Ranju
影响因子：
6.4
作者：
Bosetti, Cristina;Carioli, Greta;La Vecchia, Carlo
通讯作者：
La Vecchia, Carlo
影响因子：
9.3
作者：
Carney, Brandon;Kossatz, Susanne;Reiner, Thomas
通讯作者：
Reiner, Thomas
影响因子：
8.4
作者：
Nosho, Katsuhiko;Yamamoto, Hiroyuki;Shinomura, Yasuhisa
通讯作者：
Shinomura, Yasuhisa