Off-Peak Near-Infrared-II (NIR-II) Bioimaging of an Immunoconjugate Having Peak Fluorescence Emission in the NIR-I Spectral Region for Improving Tumor Margin Delineation.
Off-Peak Near-Infrared-II (NIR-II) Bioimaging of an Immunoconjugate Having Peak Fluorescence Emission in the NIR-I Spectral Region for Improving Tumor Margin Delineation.
复制标题
DOI：
10.1021/acsabm.0c01050
复制
发表时间：
2020-12-21
影响因子：
4.7
通讯作者：
Chin, Frederick T
中科院分区：
文献类型：
--
作者：
Hettie, Kenneth S;Teraphongphom, Nutte Tarn;Ertsey, Robert;Chin, Frederick T
恶性肿瘤的主要治疗方法仍然是切除。复发和术后预后的最强预测因素是手术切缘是否残留病变组织/细胞。癌症手术需要外科医生能够在视觉上区分细微的颜色阴影，以试图在标准白光照明下区分患病组织和健康组织，因为这样的组织状态在介观/宏观水平上看起来是相同的。因此，增强外科医生这样做的能力，使得他们能够准确地描绘肿瘤边缘是至关重要的。通过利用串联的荧光构建体，利用来自实时术中荧光发射的重叠对比伪色对术野进行颜色编码，手术引导的手术有助于增强这种能力。正在进行临床试验或经FDA批准的构建体在可见光（405 - 700 nm）或近红外-I（NIR-I）光谱区域（700-900 nm）中提供峰值荧光发射，由此组织状态之间的区分与使用发射更长波长的光的构建体同步地逐渐改善。在这里，我们通过建立肿瘤靶向免疫偶联物的可行性，在近红外-II（NIR-II）光谱区域测量其非峰值荧光发射时，通过提供更高的肿瘤与背景比（TBRs），（1000-1700 nm）。我们制备鼠肿瘤模型，施用这种免疫缀合物，并通过利用成像系统在施用前/后对这种模型进行成像，所述成像系统分别提供在NIR-I或NIR-II光谱区域中的荧光发射的采集。在这样做时，我们确定了体内TBR、离体TBR与/-外皮肤和离体生物分布，所有这些都是通过在两个光谱区域测量肿瘤部位处的免疫缀合物的荧光发射来进行的。总的来说，我们建立了使用免疫缀合物通过利用NIR-II光谱区域从具有NIR-I峰值荧光发射的荧光构建体捕获非峰值荧光发射来提供2倍更高的TBR以提供改善的肿瘤边缘描绘的可行性。
The primary treatment for malignant tumors remains to be resection. The strongest predictor of recurrence and postoperative prognosis is whether diseased tissue/cells remain(s) at the surgical margin. Cancer surgery entails surgeons having the capability to visually distinguish between subtle shades of color in attempts of differentiating between diseased tissue and healthy tissue under standard white-light illumination, as such tissue states appear identical at the meso-/macroscopic level. Accordingly, enhancing the capability of surgeons to do so such that they can accurately delineate the tumor margin is of paramount importance. Fluorescence-guided surgery facilitates in enhancing such capability by color-coding the surgical field with overlaid contrasting pseudo-colors from real-time intraoperative fluorescence emission via utilizing fluorescent constructs in tandem. Constructs undergoing clinical trials or that are FDA-approved provide peak fluorescence emission in the visible (405 – 700 nm) or near-infrared-I (NIR-I) spectral region (700–900 nm), whereby differentiation between tissue states progressively improves in sync with using constructs that emit longer wavelengths of light. Here, we repurpose the usage of such fluorescent constructs by establishing feasibility of a tumor-targeting immunoconjugate (cetuximab-IRDye800) having peak fluorescence emission at the NIR-I spectral region to provide improved tumor margin delineation by affording higher tumor-to-background ratios (TBRs) when measuring its off-peak fluorescence emission at the near-infrared-II (NIR-II) spectral region (1000–1700 nm) in in vivo applications. We prepared murine tumor models, administered such immunoconjugate, and imaged such models pre-/post-administration via utilizing imaging systems that separately afforded acquisition of fluorescence emission in the NIR-I or NIR-II spectral region. On doing so, we determined in vivo TBRs, ex vivo TBRs with/-out skin, and ex vivo biodistribution, all via measuring the fluorescence emission of the immunoconjugate at tumor site(s) at both spectral regions. Collectively, we established feasibility of using the immunoconjugate to afford improved tumor margin delineation by providing 2-fold higher TBRs via utilizing the NIR-II spectral region to capture off-peak fluorescence emission from a fluorescent construct having NIR-I peak fluorescence emission.