Levi Jelena, Das Millie, Vasanawala Minal S, Behl Deepti, Pomper Martin, Forde Patrick M, Nakajima Erica, Sayre James, Shen Bin, Cabrera Hilda, Del Mar Niko, Gullen Michele, Pierini Michele, Cox Laura, Lokre Ojaswita, Perk Timothy, Chae Hee-Don
CellSight Technologies Inc., San Francisco, California;
Department of Medicine, Stanford University, Palo Alto, California.
J Nucl Med. 2024 Dec 3;65(12):1869-1875. doi: 10.2967/jnumed.124.268253.
Despite the systemic impact of both cancer and the associated immune response, immuno-PET is predominantly centered on assessment of the immune milieu within the tumor microenvironment. The aim of this study was to assess the value of [F]F-AraG PET imaging as a noninvasive method for evaluation of system-wide immune status of patients with non-small cell lung cancer before starting immunotherapy. Eleven patients with advanced non-small cell lung cancer were imaged with [F]F-AraG before starting immunotherapy. Diagnostic [F]FDG PET/CT scans were analyzed to assess differences in the extent of disease among patients. SUV, SUV, and total SUV (SUV) from all tumor lesions, active lymph nodes, spleen, vertebral bone marrow, liver, thyroid, heart, and bowel were extracted from the baseline [F]F-AraG scans, and discriminant and Kaplan-Meier analyses were performed to test their ability to predict patient response and overall survival. The extent of the disease was variable in the patient cohort, but none of the [F]FDG biomarkers associated with tumor burden (SUV, total metabolic tumor volume, and total lesion glycolysis) was predictive of patient survival. The differences in the [F]F-AraG and [F]FDG distribution were observed both within and between lesions, confirming that they capture distinct aspects of the tumor microenvironment. Of the 3 SUV parameters studied, [F]F-AraG SUV provided a dynamic range suitable for stratifying tumors or patients according to their immune activity. [F]F-AraG SUV measured in the lumbar and sacral vertebrae differentiated between patients who progressed on therapy and those who did not with 90.9% and 81.8% accuracy, respectively. The Kaplan-Meier analysis revealed that patients with high [F]F-AraG SUV in the lumbar bone marrow had significantly lower probability of survival than those with a low signal ( = 0.0003). This study highlights the significance of assessing systemic immunity and indicates the potential of the [F]F-AraG bone marrow signal as a predictive imaging biomarker for patient stratification and treatment guidance.
尽管癌症及其相关免疫反应具有全身性影响，但免疫正电子发射断层扫描（immuno-PET）主要集中于评估肿瘤微环境内的免疫环境。本研究的目的是评估[F]F-阿糖鸟苷正电子发射断层扫描（[F]F-AraG PET）成像作为一种非侵入性方法，在开始免疫治疗前评估非小细胞肺癌患者全身免疫状态的价值。11例晚期非小细胞肺癌患者在开始免疫治疗前接受了[F]F-AraG成像。分析诊断性[F]氟代脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（[F]FDG PET/CT）扫描，以评估患者之间疾病范围的差异。从基线[F]F-AraG扫描中提取所有肿瘤病灶、活性淋巴结、脾脏、椎骨骨髓、肝脏、甲状腺、心脏和肠道的最大标准摄取值（SUVmax）、平均标准摄取值（SUVmean）和总标准摄取值（total SUV，tSUV），并进行判别分析和Kaplan-Meier分析，以测试它们预测患者反应和总生存期的能力。患者队列中的疾病范围各不相同，但与肿瘤负荷相关的[F]FDG生物标志物（SUVmax、总代谢肿瘤体积和总病灶糖酵解）均不能预测患者生存期。在病灶内和病灶间均观察到[F]F-AraG和[F]FDG分布的差异，证实它们捕捉到了肿瘤微环境的不同方面。在所研究的3个SUV参数中，[F]F-AraG SUV提供了一个适合根据肿瘤或患者免疫活性进行分层的动态范围。在腰椎和骶椎测量的[F]F-AraG SUV区分治疗进展患者和未进展患者的准确率分别为90.9%和81.8%。Kaplan-Meier分析显示，腰椎骨髓中[F]F-AraG SUV高的患者生存概率显著低于信号低的患者（P = 0.0003）。本研究强调了评估全身免疫的重要性，并表明[F]F-AraG骨髓信号作为预测性成像生物标志物在患者分层和治疗指导方面的潜力。
