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

项目摘要/摘要： 2021年，美国估计有60万人死于转移性疾病；这是早期死亡的主要原因 黑色素瘤、肺癌、乳腺癌等多种癌症患者的死亡和低生活质量 癌症，还有头颈癌。据估计，多达50%的肺癌和黑色素瘤患者 发生颅内转移性疾病。免疫检查点抑制(ICI)疗法使治疗发生了革命性的变化 通过提供另一种治疗选择来治疗转移性黑色素瘤、头颈部癌和肺癌 在终末期疾病中，并显示作为一线治疗的有效性。靶向PD-ICI的有效性 1/PD-L1轴与肿瘤细胞表面PD-L1跨膜蛋白的表达有关 肿瘤内存在浸润性淋巴细胞(TIL)。低水平PD-L1表达的肿瘤 已发现与高PD-L1的肿瘤相比，ICI治疗的反应性降低 表情。目前，PD-L1水平是通过免疫组织化学(IHC)检测的，这需要侵入性 活组织检查限制了对PD-L1表达的动态性质的评估，并可能导致抽样错误。 因此，我们的目标是使用一种新的PD-L1验证一种非侵入性的全肿瘤定量成像方法 头颈癌根治术后正电子发射断层扫描示踪研究 原发肿瘤和局部区域淋巴转移因此提供了一个很好的模型 与IHC的相关研究。我们将把这项研究扩展到脑转移患者，因为有一种 在这一人群中迫切需要对PD-L1进行非侵入性检测，因为这些病变的活检很少。在我们的研究中， 我们将为脑转移患者成像，主要来自肺癌和黑色素瘤， 计划进行活组织检查。我们研究的最终目标是验证定量PD-L1 PET成像 在不需要活检和鉴定的情况下确定PD-L1在原发癌和转移癌中的表达 PD-L1定量PET的参数，将使其转化为临床实践。然后，此方法可以 用于确定哪些患者可能从免疫疗法中受益。

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.