F-FSPG PET/CT 成像在原发性和转移性脑肿瘤患者中系统 x 转运体活性的研究。
F-FSPG PET/CT Imaging of System x Transporter Activity in Patients with Primary and Metastatic Brain Tumors.
机构信息
From the Department of Radiology, Molecular Imaging Program at Stanford (MIPS) (M.W., I.S., A.P.F., R.M., M.J., N.H., G.Z., N.F., J.R., F.T.C., S.S.G., E.S.M.), Department of Neurosurgery (N.F., S.N., G.L.), and Department of Neurology and Neurological Sciences (N.F., S.N., G.L.), Stanford University School of Medicine, Stanford, Calif; Department of Molecular and Medical Pharmacology, UCLA Ahmanson Biological Imaging Center, David Geffen School of Medicine at UCLA, Los Angeles, Calif (I.S.); Department of Biomedical Engineering, Department of Neurology, University of California, Davis, Davis, Calif (A.P.F.); Stanford Bio-X (M.W., G.Z., G.L., F.T.C., S.S.G.) and Departments of Bioengineering (S.S.G.) and Materials Science & Engineering (S.S.G.), Stanford University, Stanford, Calif; Life Molecular Imaging GmbH, Berlin, Germany (N.K., M.B., S.B., A.W.S., L.M.D.); Department of Pathology, Microbiology and Immunology (T.A.) and Department of Radiology and Radiological Sciences, Institute of Imaging Science, Center for Molecular Probes (H.C.M.), Vanderbilt University Medical Center, Nashville, Tenn; and Department of Cancer Systems Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (H.C.M.).
出版信息
Radiology. 2022 Jun;303(3):620-631. doi: 10.1148/radiol.203296. Epub 2022 Feb 22.
Background The PET tracer (4S)-4-(3-[F]fluoropropyl)-l-glutamate (F-FSPG) targets the system x cotransporter, which is overexpressed in various tumors. Purpose To assess the role of F-FSPG PET/CT in intracranial malignancies. Materials and Methods Twenty-six patients (mean age, 54 years ± 12; 17 men; 48 total lesions) with primary brain tumors ( = 17) or brain metastases ( = 9) were enrolled in this prospective, single-center study (ClinicalTrials.gov identifier: NCT02370563) between November 2014 and March 2016. A 30-minute dynamic brain F-FSPG PET/CT scan and a static whole-body (WB) F-FSPG PET/CT scan at 60-75 minutes were acquired. Moreover, all participants underwent MRI, and four participants underwent fluorine 18 (F) fluorodeoxyglucose (FDG) PET imaging. PET parameters and their relative changes were obtained for all lesions. Kinetic modeling was used to estimate the F-FSPG tumor rate constants using the dynamic and dynamic plus WB PET data. Imaging parameters were correlated to lesion outcomes, as determined with follow-up MRI and/or pathologic examination. The Mann-Whitney test or Student test was used for group mean comparisons. Receiver operating characteristic curve analysis was used for performance comparison of different decision measures. Results F-FSPG PET/CT helped identify all 48 brain lesions. The mean tumor-to-background ratio (TBR) on the whole-brain PET images at the WB time point was 26.6 ± 24.9 (range: 2.6-150.3). When F-FDG PET was performed, F-FSPG permitted visualization of non-F-FDG-avid lesions or allowed better lesion differentiation from surrounding tissues. In participants with primary brain tumors, the predictive accuracy of the relative changes in influx rate constant K and maximum standardized uptake value to discriminate between poor and good lesion outcomes were 89% and 81%, respectively. There were significant differences in the F-FSPG uptake curves of lesions with good versus poor outcomes in the primary brain tumor group ( < .05) but not in the brain metastases group. Conclusion PET/CT imaging with (4S)-4-(3-[F]fluoropropyl)-l-glutamate (F-FSPG) helped detect primary brain tumors and brain metastases with a high tumor-to-background ratio. Relative changes in F-FSPG uptake with multi-time-point PET appear to be helpful in predicting lesion outcomes. Clinical trial registration no. NCT02370563 © RSNA, 2022
背景 正电子发射断层扫描（PET）示踪剂（4S）-4-（3-[F]氟丙基）-l-谷氨酸（F-FSPG）靶向系统 x 协同转运蛋白，该蛋白在各种肿瘤中过度表达。目的 评估 F-FSPG PET/CT 在颅内恶性肿瘤中的作用。材料与方法 2014 年 11 月至 2016 年 3 月期间，在一项前瞻性单中心研究（ClinicalTrials.gov 标识符：NCT02370563）中，纳入了 26 名原发性脑肿瘤（ = 17 例）或脑转移瘤（ = 9 例）患者。每位患者均接受了 30 分钟的动态脑 F-FSPG PET/CT 扫描和 60-75 分钟的静态全身（WB）F-FSPG PET/CT 扫描。此外，所有患者均接受了 MRI 检查，4 名患者接受了氟 18（F）氟脱氧葡萄糖（FDG）PET 成像。对所有病变均获得了 PET 参数及其相对变化。使用动态和动态加 WB PET 数据对动力学模型进行了拟合，以估算 F-FSPG 肿瘤速率常数。根据随访 MRI 和/或病理检查确定病变结果，并对成像参数进行相关性分析。采用 Mann-Whitney U 检验或学生 t 检验进行组间均值比较。采用受试者工作特征曲线分析比较不同决策指标的性能。结果 F-FSPG PET/CT 有助于识别所有 48 个脑病变。在 WB 时间点的全脑 PET 图像上，平均肿瘤与背景比（TBR）为 26.6 ± 24.9（范围：2.6-150.3）。当进行 F-FDG PET 检查时，F-FSPG 可以显示非 F-FDG 摄取性病变，或者可以更好地区分病变与周围组织。在原发性脑肿瘤患者中，流入速率常数 K 和最大标准化摄取值的相对变化预测不良和良好病变结局的准确性分别为 89%和 81%。原发性脑肿瘤组中，良好结局与不良结局的病变 F-FSPG 摄取曲线存在显著差异（ <.05），而脑转移瘤组则无显著差异。结论 F-FSPG（4S）-4-（3-[F]氟丙基）-l-谷氨酸的 PET/CT 成像有助于检测原发性脑肿瘤和脑转移瘤，其肿瘤与背景比高。多时间点 PET 摄取的相对变化似乎有助于预测病变结局。临床试验注册号 NCT02370563 © RSNA，2022
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