From the Department of Radiology (M.P.S.D., W.W., J.S.L.), Department of Medicine (J.J.H., J.B., A.M.O., J.J.H., I.K.M., J.F.G., D.P.K.), Radiochemistry and Molecular Imaging Probe Core (H.Z., E.M.B., S.K.L., J.S.L.), and Department of Medical Physics (B.J.B., P.B.Z.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room S113E, New York, NY 10065; Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY (H.Z., K.S., J.S.L.); Department of Radiology, Weill-Cornell Medical College, New York, NY (M.P.S.D., W.W., J.S.L.); Laboratory of Neural Systems, the Rockefeller University, New York, NY (C.P.); Department of Pathology, University of Michigan, Ann Arbor, Mich (S.V.); and Departments of Radiology and Pharmacology, University of Pennsylvania, Philadelphia, Pa (H.F.K.).
Radiology. 2018 May;287(2):667-675. doi: 10.1148/radiol.2017162610. Epub 2018 Jan 31.
Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq ± 118, <100 μg) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P < .05 was considered indicative of a statistically significant difference. Results FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P = .07). Patients experienced no adverse effects. Conclusion Preliminary human FGln PET trial results provide clinical validation of abnormal glutamine metabolism as a potential tumor biomarker for targeted radiotracer imaging in several different cancer types. RSNA, 2018 Online supplemental material is available for this article. Clinical trial registration no. NCT01697930.
目的 评估氟 18-(2S,4R)-4-氟谷氨酸（FGln），一种谷氨酰胺类似物放射性示踪剂的临床安全性、药代动力学和肿瘤成像特征。
材料与方法 本研究经机构审查委员会批准，并根据赫尔辛基宣言和《健康保险流通与责任法案》，在美国食品和药物管理局批准的新药临床试验申请下进行。所有患者均提供书面知情同意书。2013 年 1 月至 2016 年 10 月，25 例癌症成人患者静脉注射 FGln 示踪剂（平均 244MBq±118，<100μg），随后进行正电子发射断层扫描（PET）和血放射测定。采用描述性统计方法总结患者数据。对未禁食（n=13）和禁食至少 8 小时（n=12）患者的 FGln 生物分布和血浆氨基酸水平进行非参数单向方差分析，采用 Bonferroni 校正。对有配对 PET 扫描的 15 例患者的肿瘤 FGln 摄取与氟脱氧葡萄糖（FDG）摄取进行 Fisher 确切检验。P<0.05 表示有统计学意义。
结果 在 25 例患者中的 17 例中，FGln PET 描绘了不同癌症类型（乳腺、胰腺、肾、神经内分泌、肺、结肠、淋巴瘤、胆管或神经胶质瘤）的肿瘤，主要是遗传突变导致异常谷氨酰胺代谢的侵袭性肿瘤。急性禁食对 FGln 生物分布和血浆氨基酸水平没有显著影响。FGln 摄取的肿瘤均为 FDG 摄取，但反之则不然（P=0.07）。患者无不良反应。
结论 初步的人类 FGln PET 试验结果为异常谷氨酰胺代谢作为多种不同癌症类型的靶向放射性示踪剂成像的潜在肿瘤生物标志物提供了临床验证。
放射学学会，2018 年
在线补充材料可在本文中获取。临床试验注册号：NCT01697930。
