Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
J Nucl Med. 2013 Jan;54(1):117-23. doi: 10.2967/jnumed.112.108704. Epub 2012 Dec 11.
(4S)-4-(3-(18)F-fluoropropyl)-l-glutamate ((18)F-FSPG, or BAY 94-9392) is a new tracer to assess system x(C)(¯) transporter activity with PET. The aim of this study was to explore the tumor detection rate of (18)F-FSPG, compared with that of (18)F-FDG, in patients with hepatocellular carcinoma (HCC).
Preclinically, in vivo HCC models of orthotopically implanted Huh7 and MH3924a cancer cells were studied with (18)F-FSPG in Naval Medical Research Institute nude mice (n = 3) and August-Copenhagen Irish rats (n = 4), respectively. Clinically, 5 patients with HCC who had hyper- or isometabolic lesions on (18)F-FDG PET were enrolled for evaluation of the tracer. Dynamic whole-body PET images with (18)F-FSPG were acquired for up to 120 min after injection of approximately 300 MBq of (18)F-FSPG. Immunohistochemical expression levels of the xCT subunit of the system x(C)(¯) and CD44 of HCC were studied in 4 patients with HCC.
Strong tumor uptake and low background from nontarget tissue allowed excellent tumor visualization in animal models with orthotopically implanted liver tumors. (18)F-FSPG PET procedures were well tolerated in all patients. (18)F-FSPG PET and (18)F-FDG detected lesions in 5 of 5 and 3 of 5 patients, respectively. The maximal standardized uptake values (SUV) were comparable ((18)F-FSPG, 4.7 ± 3.2; (18)F-FDG, 6.1 ± 2.9). The ratios of maximal SUV of the tumor to mean SUV of normal liver were also comparable ((18)F-FSPG, 3.6 ± 2.2; (18)F-FDG, 2.7 ± 1.3), but the mean SUV of normal liver of (18)F-FSPG was significantly lower than that of (18)F-FDG (P < 0.05). Two patients with HCC who showed both xCT and CD44 expression had moderate or intense accumulation of (18)F-FSPG, but the remaining 2 patients with negative CD44 expression showed mild uptake.
(18)F-FSPG was successfully translated from preclinical evaluation into patients with HCC. (18)F-FSPG may be a promising tumor PET agent with a high cancer detection rate in patients with HCC.
本研究旨在比较新型正电子发射断层扫描（PET）示踪剂（4S）-4-（3-（18）F-氟丙基）-L-谷氨酸（（18）F-FSPG，或 BAY 94-9392）与（18）F-FDG 在肝细胞癌（HCC）患者中的肿瘤检出率。
在临床前研究中，我们分别在海军医学研究所裸鼠（n=3）和 August-Copenhagen Irish 大鼠（n=4）的原位植入 Huh7 和 MH3924a 癌细胞的 HCC 模型中，用（18）F-FSPG 进行了研究。在临床研究中，我们招募了 5 例在（18）F-FDG PET 上显示高代谢或等代谢病灶的 HCC 患者，以评估该示踪剂。在注射约 300MBq（18）F-FSPG 后，对患者进行长达 120 分钟的全身动态 PET 扫描。在 4 例 HCC 患者中，我们还研究了 HCC 中系统 x(C)(-)的 xCT 亚基和 CD44 的免疫组织化学表达水平。
在原位植入的肝肿瘤动物模型中，肿瘤摄取高，非靶组织背景低，因此能够很好地显示肿瘤。所有患者均能耐受（18）F-FSPG PET 检查。（18）F-FSPG PET 和（18）F-FDG 分别在 5 例和 3 例患者中检测到病灶。最大标准化摄取值（SUV）相似（（18）F-FSPG，4.7±3.2；（18）F-FDG，6.1±2.9）。肿瘤的最大 SUV 与正常肝的平均 SUV 的比值也相似（（18）F-FSPG，3.6±2.2；（18）F-FDG，2.7±1.3），但（18）F-FSPG 的正常肝 SUV 均值明显低于（18）F-FDG（P<0.05）。2 例具有 xCT 和 CD44 表达的 HCC 患者的（18）F-FSPG 摄取为中度或强烈，而另外 2 例 CD44 表达阴性的患者摄取为轻度。
（18）F-FSPG 已从临床前评估成功转化为 HCC 患者的临床应用。（18）F-FSPG 可能是一种很有前途的肿瘤 PET 示踪剂，在 HCC 患者中有很高的肿瘤检出率。
