Petrulli Joseph Ryan, Zheng Mingqiang, Huang Yiyun, Nabulsi Nabeel B, Goldberg Sarah B, Contessa Joseph N, Morris Evan D
Department of Biomedical Engineering, Yale University New Haven, CT, United States.
Department of Radiology and Biomedical Imaging, Yale University New Haven, CT, United States.
Am J Nucl Med Mol Imaging. 2021 Apr 15;11(2):143-153. eCollection 2021.
[C]-Erlotinib is a radiolabeled analogue of a tyrosine kinase inhibitor used to treat non-small cell lung cancer (NSCLC) which expresses specific kinase domain mutations of the epidermal growth factor receptor (EGFR). In this study, 10 subjects with NSCLC and assorted EGFR mutation status underwent a dynamic, multi-bed positron emission tomography (PET) scan using [C]-erlotinib. Data were analyzed using a variety of quantitative techniques common in PET (graphical methods, kinetic models, and uptake value-based endpoints). Our primary goal was to determine the most reliable imaging endpoint given the need for maintaining minimal patient burden and recognizing the advantage of simple calculations in future trials.
Standard uptake values (a semi-quantitative endpoint) were well correlated with both binding potential and volume of distribution (fully quantitative endpoints). Normalized tracer uptake was found to stabilize approximately 60 minutes post tracer injection. : The kinetic properties of [C]-erlotinib varied greatly across subjects. Our novel scanning protocol produced an important dataset which highlights the great heterogeneity of NSCLC and its apparent impact on [C]-erlotinib kinetics. A lack of correlation between EGFR mutational status and quantitative endpoints appears to be due to disease heterogeneity and low tracer uptake. The most reliable fits of the dynamic data were based on the one-tissue compartmental model which were well correlated with mean SUV. Due to this correlation and good stability at late-time, SUV seems sufficiently well-suited to quantitative imaging of NSCLC lesions in the whole body with [C]-erlotinib.
[碳]-厄洛替尼是一种酪氨酸激酶抑制剂的放射性标记类似物，用于治疗表达表皮生长因子受体（EGFR）特定激酶结构域突变的非小细胞肺癌（NSCLC）。在本研究中，10名患有NSCLC且具有不同EGFR突变状态的受试者使用[碳]-厄洛替尼进行了动态、多床位正电子发射断层扫描（PET）。使用PET中常见的多种定量技术（图形方法、动力学模型和基于摄取值的终点）对数据进行了分析。我们的主要目标是在需要尽量减轻患者负担并认识到在未来试验中简单计算的优势的情况下，确定最可靠的成像终点。
标准摄取值（一种半定量终点）与结合潜能和分布容积（完全定量终点）均具有良好的相关性。发现示踪剂注射后约60分钟归一化示踪剂摄取趋于稳定。[碳]-厄洛替尼的动力学特性在受试者之间差异很大。我们新颖的扫描方案产生了一个重要的数据集，突出了NSCLC的巨大异质性及其对[碳]-厄洛替尼动力学的明显影响。EGFR突变状态与定量终点之间缺乏相关性似乎是由于疾病异质性和示踪剂摄取较低。动态数据的最可靠拟合基于单组织室模型，其与平均SUV具有良好的相关性。由于这种相关性以及后期的良好稳定性，SUV似乎非常适合用[碳]-厄洛替尼对全身NSCLC病变进行定量成像。
