Dual-Function Antibody Conjugate-Enabled Photoimmunotherapy Complements Fluorescence and Photoacoustic Imaging of Head and Neck Cancer Spheroids.

Dual-Function Antibody Conjugate-Enabled Photoimmunotherapy Complements Fluorescence and Photoacoustic Imaging of Head and Neck Cancer Spheroids.
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DOI:
10.1021/acs.bioconjchem.3c00406
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发表时间:
2024-01-17
影响因子:
4.7
通讯作者:
Hasan, Tayyaba
Hasan, Tayyaba
中科院分区:
化学2区
文献类型:
--
作者:
Saad, Mohammad A.;Grimaldo-Garcia, Stacey;Sweeney, Allison;Mallidi, Srivalleesha;Hasan, Tayyaba

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几种分子靶向成像和治疗剂正在进行头颈部癌症的图像引导手术和光免疫治疗(PIT)的临床试验。在此背景下,我们已经报道了一种用于EGFR高表达癌细胞的多模式成像和光免疫治疗(PIT)的双功能抗体结合物(DFAC)的开发、表征和特异性。先前报道的和本研究中使用的DFAC包括EGFR靶向抗体西妥昔单抗,用于荧光成像和PIT的连接到苯并卟啉衍生物(BPD)的西妥昔单抗,以及用于光声成像的以硅为中心的萘菁染料。我们报告了DFAC在利用荧光和光声成像检测微小癌球体方面的评价和性能,以及它们在PIT治疗中的作用。我们证明,虽然荧光成像可以检测到体积大于0.049毫立方米的球体,但基于光声成像的检测即使是研究中开发的最小的球体(0.01mm3)也是可能的。当接受PIT时,球体表现出剂量依赖的反应,较小的球体(0.01和0.018 mm~3)在100J/cm~2处理时显示完全反应,没有复发。总之,我们的结果证明了DFAC的互补成像和治疗能力。这可能使荧光成像能够在宏观范围内评估肿瘤的存在,随后光声成像用于描绘肿瘤边缘,指导手术切除和在单一术中通过PIT消除任何残留的微观疾病。
Several molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) for head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual-function antibody conjugate (DFAC) for multimodal imaging and photoimmunotherapy (PIT) of EGFR-overexpressing cancer cells. The DFAC reported previously and used in the present study comprises an EGFR-targeted antibody, cetuximab, conjugated to benzoporphyrin derivative (BPD) for fluorescence imaging and PIT and a Si-centered naphthalocyanine dye for photoacoustic imaging. We report here the evaluation and performance of DFAC in detecting microscopic cancer spheroids by fluorescence and photoacoustic imaging along with their treatment by PIT. We demonstrate that while fluorescence imaging can detect spheroids with volumes greater than 0.049 mm3, photoacoustic imaging-based detection was possible even for the smallest spheroids (0.01 mm3) developed in the study. When subjected to PIT, the spheroids showed a dose-dependent response, with smaller spheroids (0.01 and 0.018 mm3) showing a complete response with no recurrence when treated with 100 J/cm2. Together our results demonstrate the complementary imaging and treatment capacity of DFAC. This potentially enables fluorescence imaging to assess the presence of tumor on a macroscopic scale, followed by photoacoustic imaging for delineating tumor margins guiding surgical resection and elimination of any residual microscopic disease by PIT, in a single intraoperative setting.
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发表时间: 2014-07-08
期刊: Journal of visualized experiments : JoVE
影响因子: --
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DOI: 10.6004/jnccn.2022.0016
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