Translation and validation of non-invasive measurement of PD-L1 levels with positron emission tomography (PET) in head and neck malignancies and intracranial metastases

项目总结/摘要： 到2021年，估计美国将有60万人死于转移性疾病;这是早期癌症的主要原因。 患有各种癌症的患者死亡和生活质量差，包括黑色素瘤、肺癌、乳腺癌、 癌症和头颈癌。据估计，高达50%的肺癌和黑色素瘤患者 颅内转移性疾病。免疫检查点抑制剂（ICI）疗法彻底改变了治疗方法 转移性黑色素瘤，头颈癌和肺癌，通过提供替代治疗选择， 在终末期疾病中，并证明作为一线治疗的有效性。ICI靶向PD的有效性- 1/PD-L1轴与肿瘤细胞表面PD-L1跨膜蛋白的表达相关 以及肿瘤内浸润淋巴细胞（TIL）的存在。表达低水平PD-L1的肿瘤 已经发现与具有高PD-L1的肿瘤相比， 表情目前，PD-L1水平是使用免疫组织化学（IHC）测量的，这需要有创性的免疫组织化学检测。 活检限制了PD-L1表达动态性质的评价，并可能导致采样错误。 因此，我们的目标是验证一种使用新型PD-L1的非侵入性全肿瘤定量成像方法。 正电子发射断层扫描（PET）示踪剂在接受切除术的头颈癌患者中的应用 原发性肿瘤和局部淋巴结转移，从而提供了极好的模型来进行 与IHC相关的研究。我们将把这项研究扩展到脑转移患者，因为 该人群迫切需要进行非侵入性PD-L1检测，因为这些病变的活检很少。在我们的研究中， 我们将对患有脑转移的患者进行成像，这些患者主要来自肺癌和黑色素瘤， 计划进行活检。我们研究的最终目标是验证定量PD-L1 PET成像 在不需要活检的情况下确定原发性和转移性癌症中的PD-L1表达， PD-L1定量PET的参数，这将使其转化为临床实践。这种方法可以 用于确定哪些患者可以从免疫治疗中受益。

PROJECT SUMMARY/ABSTRACT: In 2021, 600,000 people are estimated to die in the US from metastatic disease; the leading cause of early death and poor quality of life in patients with a variety of cancers including melanoma, lung cancer, breast cancer, and head and neck cancer. Up to 50% of patients with lung cancer and melanoma are estimated to develop intracranial metastatic disease. Immune checkpoint inhibitor (ICI) therapy has revolutionized treatment of metastatic melanoma, head and neck cancer, and lung cancer by providing an alternative treatment option in end-stage disease and demonstrating effectiveness as a first line therapy. Effectiveness of ICI targeting PD- 1/PD-L1 axis has been associated with the expression of PD-L1 transmembrane protein on tumor cell surface and the presence of infiltrating lymphocytes (TILs) within the tumor. Tumors expressing low levels of PD-L1 have been found to have decreased response to ICI therapy as compared to tumors with high PD-L1 expression. Currently, PD-L1 levels are measured using immunohistochemistry (IHC), which require invasive biopsies that limit evaluation of the dynamic nature of PD-L1 expression and can cause sampling errors. Therefore, we aim to validate a non-invasive quantitative imaging method of whole tumors using a novel PD-L1 positron emission tomography (PET) tracer in patients with head and neck cancer who undergo resection of primary tumor and locoregional lymph node metastases thus providing an excellent model to perform correlative studies with IHC. We will extend the study to patients with brain metastases because there is a critical need for a non-invasive test for PD-L1 in this population, as biopsy of these lesions is rare. In our study, we will image patients with brain metastases, which are predominantly from lung cancer and melanoma, that are planned to undergo biopsy. The ultimate goal of our research is to validate quantitative PD-L1 PET imaging in determining PD-L1 expression within primary and metastatic cancer without the need for biopsy and identify parameters of PD-L1 quantitative PET that will allow its translation into clinical practice. This method can then be used to determine which patients may benefit from immunotherapy.