Saad Mohammad A, Grimaldo-Garcia Stacey, Sweeney Allison, Mallidi Srivalleesha, Hasan Tayyaba
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Middlebury College, Middlebury, VT 05753, USA.
bioRxiv. 2023 Feb 2:2023.01.30.526194. doi: 10.1101/2023.01.30.526194.
Several molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) of head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual function antibody conjugate (DFAC) for multi-modal imaging and photoimmunotherapy (PIT) of EGFR over-expressing cancer cells. The DFAC reported previously and used in the present study, comprises of 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 mm, photoacoustic imaging-based detection was possible even for the smallest spheroids (0.01 mm), developed in the study. When subjected to PIT, the spheroids showed a dose-dependent response with smaller spheroids (0.01 and 0.018 mm) showing a complete response with no recurrence when treated with 100 J/cm. Together our results demonstrate the complementary imaging and treatment capacity of DFAC. This potentially enables fluorescence imaging to assess tumor presence 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 intra-operative setting.
几种分子靶向成像和治疗剂正在进行临床试验，用于头颈部癌症的影像引导手术和光免疫疗法（PIT）。在此背景下，我们之前报道了一种双功能抗体偶联物（DFAC）的研发、特性及特异性，该偶联物用于过表达表皮生长因子受体（EGFR）癌细胞的多模态成像和光免疫疗法（PIT）。之前报道并用于本研究的DFAC，由一种与用于荧光成像和PIT的苯并卟啉衍生物（BPD）偶联的EGFR靶向抗体——西妥昔单抗，以及一种用于光声成像的硅中心萘酞菁染料组成。我们在此报告DFAC通过荧光和光声成像检测微小癌球状体以及通过PIT对其进行治疗的评估和性能。我们证明，虽然荧光成像能够检测体积大于0.049立方毫米的球状体，但基于光声成像的检测对于本研究中所培养的最小球状体（0.01立方毫米）也是可行的。当进行PIT时，球状体呈现剂量依赖性反应，较小的球状体（0.01和0.018立方毫米）在用100焦耳/平方厘米进行治疗时显示出完全反应且无复发。我们总的研究结果证明了DFAC在成像和治疗方面的互补能力。这有可能使荧光成像在宏观尺度上评估肿瘤的存在，随后通过光声成像描绘肿瘤边缘以指导手术切除，并在单一术中环境中通过PIT消除任何残留的微小疾病。
