1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, China.
2 Department of Nuclear Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Mol Imaging. 2019 Jan-Dec;18:1536012118821032. doi: 10.1177/1536012118821032.
To evaluate the preclinical value of F-fluoropropionic acid (F-FPA) and F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) for imaging HCCs.
The F-FPA and F-FDG uptake patterns in 3 HCC cell lines (Hep3B, HepG2, and SK-Hep1) were assessed in vitro and in vivo. The F-FPA uptake mechanism was investigated using inhibition experiments with orlistat and 5-tetradecyloxy-2-furoic acid. The F-FPA PET imaging was performed in different tumor animal models and compared with F-FDG. We also evaluated the expressions of glucose transporter-1 (GLUT1), fatty acid synthase (FASN), and matrix metalloproteinase-2 (MMP2) in these cell lines.
In vitro experiments showed that the radiotracer uptake patterns were complementary in the HCC cell lines. Orlistat and 5-tetradecyloxy-2-furoic acid decreased the uptake of F-FPA. The tumor-to-liver ratio of F-FPA was superior to that of F-FDG in the SK-Hep1 and HepG2 tumors ( P < .05). However, in the Hep3B tumors, the tumor-to-liver normalized uptake of F-FDG was higher than F-FPA ( P < .01). FASN was highly expressed in cell lines with high F-FPA uptake, whereas GLUT1 was highly expressed in cell lines with high F-FDG uptake. The F-FPA uptake correlated with FASN ( r = 0.89, P = .014) and MMP2 ( r = 0.77, P = .002) expressions.
PET imaging with F-FPA combined with F-FDG can be an alternative for detecting HCC.
评估 F-氟丙酸(F-FPA)和 F-氟脱氧葡萄糖(F-FDG)正电子发射断层扫描(PET)在 HCC 成像中的临床前价值。
在体外和体内评估了 3 种 HCC 细胞系(Hep3B、HepG2 和 SK-Hep1)中 F-FPA 和 F-FDG 的摄取模式。通过使用奥利司他和 5-十四烷氧基-2-糠酸进行抑制实验,研究了 F-FPA 摄取机制。在不同的肿瘤动物模型中进行了 F-FPA PET 成像,并与 F-FDG 进行了比较。我们还评估了这些细胞系中葡萄糖转运蛋白 1(GLUT1)、脂肪酸合酶(FASN)和基质金属蛋白酶 2(MMP2)的表达。
体外实验表明,示踪剂在 HCC 细胞系中的摄取模式是互补的。奥利司他和 5-十四烷氧基-2-糠酸降低了 F-FPA 的摄取。F-FPA 的肿瘤与肝脏比值在 SK-Hep1 和 HepG2 肿瘤中优于 F-FDG(P<0.05)。然而,在 Hep3B 肿瘤中,F-FDG 的肿瘤与肝脏归一化摄取高于 F-FPA(P<0.01)。FASN 在 F-FPA 摄取较高的细胞系中高度表达,而 GLUT1 在 F-FDG 摄取较高的细胞系中高度表达。F-FPA 的摄取与 FASN(r=0.89,P=0.014)和 MMP2(r=0.77,P=0.002)的表达相关。
F-FPA 与 F-FDG 联合 PET 成像可以作为检测 HCC 的替代方法。