Purpose: Elevated glucose uptake is a hallmark of cancer. Fluorodeoxyglucose (FDG) uptake was believed to indicate the aggressiveness of tumors and the standardized uptake value (SUV) is a well-known measurement for FDG uptake in positron emission tomography-computed tomography (PET/CT). However, the SUV is variable due to the heterogeneity of tumors. Methods: 126 patients with colorectal cancer underwent ¹⁸F-FDG PET/CT scanning before surgery between Jan 2011 and April 2016. Cancer-associated fibroblast (CAF) densities were calculated with the inForm Advanced image analysis software and were comparatively analyzed between patients with high and low maximum SUV (SUVmax-high and SUVmax-low). Glucose uptake was evaluated in induced and isolated CAFs and CAF-cocultured colon cancer HCT116 cells. Moreover, micro-PET/CT was performed on xenografted tumors and autoradiography was performed in the AOM/DSS induced colon cancer model. Results: CAFs were glycolytic, evidenced by glucose uptake and upregulated HK2 expression. Compared to non-activated fibroblasts (NAFs), CAFs were more dependent on glucose and sensitive to a glycolysis inhibitor. CAFs increased the SUVmax in xenograft tumors and spontaneous colon cancers. Moreover, multivariate analysis revealed that the SUVmax was only associated with tumor size among conventional parameters in colon cancer patients (126 cases, p = 0.009). Besides tumor size, the CAF density was the critical factor associated with SUVmax and outcome, which was 2.27 ± 0.74 and 1.68 ± 0.45 in the SUVmax-high and the SUVmax-low groups, respectively (p = 0.014). Conclusion: CAFs promote tumor progression and increase SUVmax of ¹⁸F-FDG, suggesting CAFs lead to the intratumor heterogeneity of the SUV and the SUVmax is a prognostic marker for cancer patients.

中文翻译：

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癌症相关的成纤维细胞可增强肿瘤¹⁸ F-FDG的摄取并有助于PET-CT的肿瘤内异质性

目的：葡萄糖摄取增加是癌症的标志。氟代葡萄糖（FDG）的摄取被认为表明了肿瘤的侵袭性，而标准化摄取值（SUV）是正电子发射断层扫描计算机断层扫描（PET / CT）中FDG摄取的众所周知的测量方法。然而，由于肿瘤的异质性，SUV是可变的。方法： 126例大肠癌患者接受了^18例在2011年1月至2016年4月之间进行术前F-FDG PET / CT扫描。使用inForm Advanced图像分析软件计算了与癌症相关的成纤维细胞（CAF）密度，并对最高和较低最大SUV（SUVmax-high和SUVmax）患者进行了比较分析。 SUVmax-低）。在诱导和分离的CAF和CAF共培养的结肠癌HCT116细胞中评估了葡萄糖摄取。此外，对异种移植肿瘤进行了微型PET / CT，在AOM / DSS诱导的结肠癌模型中进行了放射自显影。结果：CAF具有糖酵解作用，可通过葡萄糖摄取和HK2表达上调来证明。与未激活的成纤维细胞（NAF）相比，CAF更依赖于葡萄糖并且对糖酵解抑制剂敏感。CAFs增加了异种移植肿瘤和自发性结肠癌中的SUVmax。此外，多变量分析表明，在结肠癌患者的常规参数中，SUVmax仅与肿瘤大小有关（126例，p = 0.009）。除了肿瘤大小以外，CAF密度是与SUVmax和预后相关的关键因素，在SUVmax高和SUVmax低的组分别为2.27±0.74和1.68±0.45（p = 0.014）。结论： CAFs促进肿瘤进展并增加^18的SUVmax。F-FDG提示CAF导致SUV的肿瘤内异质性，而SUVmax是癌症患者的预后指标。