Kwee Sandi A, Okimoto Gordon S, Chan Owen Tm, Tiirikainen Maarit, Wong Linda L
Cancer Biology Program, The University of Hawaii Cancer CenterHonolulu, Hawaii, USA; Hamamatsu/Queen's PET Imaging Center, The Queen's Medical CenterHonolulu, Hawaii, USA.
Cancer Biology Program, The University of Hawaii Cancer Center Honolulu, Hawaii, USA.
Am J Nucl Med Mol Imaging. 2016 Jan 28;6(1):73-83. eCollection 2016.
PET using fluorine-18 fluorocholine ((18)F-fluorocholine) may detect malignancies that involve altered choline metabolism. While (18)F-fluorocholine PET/CT has shown greater sensitivity for detecting hepatocellular carcinoma (HCC) than (18)F-fluoro-D-deoxyglucose (FDG) PET/CT, it is not known whether it can also detect intrahepatic cholangiocarcinoma (ICC), a less common form of primary liver cancer. Clinical, radiographic, and histopathologic data from 5 patients with ICC and 23 patients with HCC from a diagnostic trial of liver (18)F-fluorocholine PET/CT imaging were analyzed to preliminarily evaluate (18)F-fluorocholine PET/CT for ICC. Imaging was correlated with whole-genome expression profiling to identify molecular pathways associated with tumor phenotypes. On PET/CT, all ICC tumors demonstrated low (18)F-fluorocholine uptake with a significantly lower tumor to mean background uptake ratio than HCC tumors (0.69 vs. 1.64, p < 0.0001), but no corresponding significant difference in liver parenchyma uptake of (18)F-fluorocholine between ICC and HCC patients (8.0 vs. 7.7, p = 0.74). Two ICC patients demonstrated increased tumor metabolism on FDG PET/CT, while immunohistochemical analysis of ICC tumors revealed overexpression of glucose transporter 1 (GLUT-1) and hexokinase indicating a hyper-glycolytic phenotype. Gene expression analysis revealed down-regulation of farnesoid-X-receptor and other lipid pathways in ICC relative to HCC, and up-regulation of glycolytic pathways and GLUT-1 by HIF1α. These results imply limited utility of (18)F-fluorocholine in ICC, however, significant metabolic differences between ICC, HCC, and parenchymal liver tissue may still provide clues about the underlying liver pathology. Gene and protein expression analysis support hyperglycolysis as a more dominant metabolic trait of ICC.
使用氟 - 18氟胆碱（（18）F - 氟胆碱）的正电子发射断层扫描（PET）可能检测出涉及胆碱代谢改变的恶性肿瘤。虽然（18）F - 氟胆碱PET/CT在检测肝细胞癌（HCC）方面比（18）F - 氟代脱氧葡萄糖（FDG）PET/CT表现出更高的灵敏度，但尚不清楚它是否也能检测肝内胆管癌（ICC），这是一种不太常见的原发性肝癌形式。分析了来自肝脏（18）F - 氟胆碱PET/CT成像诊断试验的5例ICC患者和23例HCC患者的临床、影像学和组织病理学数据，以初步评估（18）F - 氟胆碱PET/CT对ICC的诊断价值。将成像与全基因组表达谱进行关联，以识别与肿瘤表型相关的分子途径。在PET/CT上，所有ICC肿瘤均表现出低（18）F - 氟胆碱摄取，肿瘤与平均背景摄取比值显著低于HCC肿瘤（0.69对1.64，p < 0.0001），但ICC和HCC患者之间肝脏实质对（18）F - 氟胆碱的摄取无相应显著差异（8.0对7.7，p = 0.74）。两名ICC患者在FDG PET/CT上显示肿瘤代谢增加，而ICC肿瘤的免疫组织化学分析显示葡萄糖转运蛋白1（GLUT - 1）和己糖激酶过表达，表明存在高糖酵解表型。基因表达分析显示，与HCC相比，ICC中法尼醇X受体和其他脂质途径下调，而HIF1α上调糖酵解途径和GLUT - 1。这些结果表明（18）F - 氟胆碱在ICC中的应用有限，然而，ICC、HCC和肝脏实质组织之间显著的代谢差异仍可能为潜在的肝脏病理提供线索。基因和蛋白质表达分析支持高糖酵解是ICC更主要的代谢特征。
