Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW.
Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW.
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DOI：
10.3389/fonc.2022.853660
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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使用荧光团 IRDye800CW 抗体偶联物的荧光图像引导手术 (IGS) 彻底改变了肿瘤减灭手术。西妥昔单抗是一种抗表皮生长因子受体 (EGFR) 单克隆抗体，与 IRDye800CW (Cet-IRDye800) 结合，是第一个用于头颈癌患者 IGS 的分子靶向抗体探针。除了手术减瘤之外，西妥昔单抗靶向光动力疗法（光免疫疗法；PIT）正在临床上出现，作为头颈部肿瘤光破坏的强大方式。许多其他光敏剂也正在进行基于光动力疗法的头颈癌的临床试验。考虑到亚治疗光动力疗法（即光动力启动（PDP））的血管和基质调节作用，本研究探讨了 PDP 和 IGS 之间的潜在协同作用，以实现新型光动力图像引导手术（P-IGS）策略。据我们所知，这是首次证明肿瘤微环境的 PDP 可以增强全长抗体（即 Cet-IRDye800）的肿瘤递送。在这项研究中，我们证明了一个概念验证，即 PDP 通过将 Cet-IRDye800 的递送增加高达 138.6%、将其间质积累加快 10.5 倍以及在 Cet-IRDye800 给药后 1 小时将其肿瘤覆盖率增加 49.5%，从而启动小鼠体内的原位 FaDu 人类头颈肿瘤以进行 P-IGS。重要的是，PDP 在 1 小时内将邻近唾液腺肿瘤检测的诊断准确性提高了 264.2%。因此，PDP 将平台期时间从 25.7 小时缩短至 2.5 小时，缩短了 10 倍，从而提供了手术时间方面的优势。因此，我们建议术前 PDP 方案可以加快并提高 IGS 介导的头颈部肿瘤减瘤手术的准确性，并缩短 IGS 时间。此外，这种 P-IGS 方案还可以实现前瞻性的术后方案，用于手术床上不可切除的微观疾病的光破坏。除此之外，PDP 在实体瘤诊断、治疗诊断和治疗抗体的同质递送中的作用对于更广泛的社区具有相当重要的意义。
Fluorescence image-guided surgery (IGS) using antibody conjugates of the fluorophore IRDye800CW have revolutionized the surgical debulking of tumors. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, conjugated to IRDye800CW (Cet-IRDye800) is the first molecular targeted antibody probe to be used for IGS in head and neck cancer patients. In addition to surgical debulking, Cetuximab-targeted photodynamic therapy (photoimmunotherapy; PIT) is emerging in the clinic as a powerful modality for head and neck tumor photodestruction. A plethora of other photoactivable agents are also in clinical trials for photodynamic-based therapies of head and neck cancer. Considering the vascular and stromal modulating effects of sub-therapeutic photodynamic therapy, namely photodynamic priming (PDP), this study explores the potential synergy between PDP and IGS for a novel photodynamic image-guided surgery (P-IGS) strategy. To the best of our knowledge, this is the first demonstration that PDP of the tumor microenvironment can augment the tumor delivery of full-length antibodies, namely Cet-IRDye800. In this study, we demonstrate a proof-of-concept that PDP primes orthotopic FaDu human head and neck tumors in mice for P-IGS by increasing the delivery of Cet-IRDye800 by up to 138.6%, by expediting its interstitial accumulation by 10.5-fold, and by increasing its fractional tumor coverage by 49.5% at 1 h following Cet-IRDye800 administration. Importantly, PDP improves the diagnostic accuracy of tumor detection by up to 264.2% with respect to vicinal salivary glands at 1 h. As such, PDP provides a time-to-surgery benefit by reducing the time to plateau 10-fold from 25.7 h to 2.5 h. We therefore propose that a pre-operative PDP regimen can expedite and augment the accuracy of IGS-mediated surgical debulking of head and neck tumors and reduce the time-to-IGS. Furthermore, this P-IGS regimen, can also enable a forward-looking post-operative protocol for the photodestruction of unresectable microscopic disease in the surgical bed. Beyond this scope, the role of PDP in the homogenous delivery of diagnostic, theranostic and therapeutic antibodies in solid tumors is of considerable significance to the wider community.
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影响因子：
3.1
作者：
Marshall, Milton V.;Draney, Daniel;Sevick-Muraca, Eva M.;Olive, D. Michael
通讯作者：
Olive, D. Michael
DOI：
10.1002/hed.23980
发表时间：
2016-04-01
影响因子：
2.9
作者：
Atallah, Ihab;Milet, Clement;Righini, Christian Adrien
通讯作者：
Righini, Christian Adrien
影响因子：
3.3
作者：
Kercher, Eric M.;Nath, Shubhankar;Spring, Bryan Q.
通讯作者：
Spring, Bryan Q.
影响因子：
3.9
作者：
Miller, Sarah E.;Tummers, Willemieke S.;Rosenthal, Eben L.
通讯作者：
Rosenthal, Eben L.
影响因子：
7.5
作者：
通讯作者：
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