^(18)F-FAPI PET/CT可视化癌症相关成纤维细胞和免疫细胞表达以及在鉴别诊断中的价值

^(18)F-FAPI PET/CT visualization of cancer-associated fibroblasts and immune cells and its application in differential diagnosis

目的研究直肠癌肿瘤组织中^(18)F-成纤维细胞激活蛋白抑制剂(FAPI)-04正电子发射断层扫描/计算机断层扫描(PET/CT)的生物学分布与肿瘤相关成纤维细胞(CAF)相关蛋白和免疫标志物表达的关系,同时探索^(18)F-FAPI-04在鉴别诊断中的应用价值。方法采用单中心前瞻性研究方法,选择2021-07-01-2022-08-30山东省肿瘤医院20例直肠癌手术患者和2例胰腺癌患者为研究对象,术前5 d内接受^(18)F-FAPI-04 PET/CT扫描,对2例同时接受FAPI和氟脱氧葡萄糖(FDG)扫描的胰腺癌患者图像进行鉴别诊断,2次扫描间隔时间≤3 d。使用核医学信息系统生成最大标准摄取值(SUV_(max))、平均标准摄取值(SUV_(mean))、肿瘤代谢体积(MTV)和总病变成纤维细胞激活蛋白(FAP)表达(TLF)。术后肿瘤标本行免疫组化染色,包括CAF相关蛋白、成纤维细胞活化蛋白(FAP)、α平滑肌肌动蛋白(α-SMA)、血小板衍生生长因子受体(PDGFR)α/β、S100A4和波形蛋白(Vimentin),以及免疫标志物CD8和CD163。采用Spearman等级相关检验评估^(18)F-FAPI-04 PET/CT摄取变量与CAF相关指标及免疫指标之间的相关性。结果FAPI摄取变量SUV_(mean)与FAP(r=0.65,P=0.020)、α-SMA(r=0.54,P=0.014)、PDGFRα/β(r=0.72,P=0.001)S100A4(r=0.76,P<0.001)和Vimentin(r=0.63,P=0.003)均有统计学意义的关联。FAPI摄取变量SUV_(max)和MTV与CAF相关蛋白的表达(FAP、α-SMA、PDGFRα/β、S100A4和Vimentin)同样具有统计学意义的正相关。FAPI摄取变量SUV_(mean)与CD8(r=-0.48,P=0.032)和CD163(r=-0.55,P=0.012)呈低度负相关。FAPI摄取变量SUV_(max)、MTV和TLF与免疫标志物CD8和CD163同样具有低度负相关。结论^(18)F-FAPI-04 PET/CT摄取变量能够可视化CAF相关蛋白的表达,并与免疫标志物相关,这可能为临床上识别高危患者早期强化治疗和识别接受免疫治疗患者的潜力提供一定的指导。^(18)F-FAPI-04 PET/CT相比较^(18)F-FDG-PET/CT具有更好的肝肿瘤背景比,识别肝转移更清晰,同时在检测淋巴结转移方面的特异性更高。

Objective To investigate whether the biodistribution of ^(18)F-fibroblast activation protein inhibitor(FAPI)-04-positron emission tomography/computed tomography(PET/CT) reflects the expression of cancer-associated fibroblast(CAF)-associated proteins and immune markers in rectal cancer tumor tissue, and to explore the application value of ^(18)F-FAPI-04 in differential diagnosis.Methods In this study, a total of 20 patients with rectal cancer underwent ^(18)F-FAPI-04 PET/CT scanning within 5 days before operation, and the images of two patients with pancreatic cancer who received FAPI and fluorodeoxygiucose(FDG) scanning at the same time were used for differential diagnosis, interval between the two scans did not exceed 3 days.The maximum standardized uptake value(SUV_(max)),mean uptake value(SUV_(mean)),tumor metabolic volume(MTV) and total lesion fibroblast activation protein(FAP) expression(TLF) were generated using a nuclear medicine information system.Postoperative tumor specimens were undergone immunohistochemical staining,including CAF-related proteins,FAP,S100A4,Vimentin,platelet-derived growth factor receptor(PDGFR)α/β,andα-smooth muscle actin(SMA),as well as immune markers CD8 and CD163.Spearman rank correlation test was used to evaluate the correlation between ^(18)F-FAPI-04PET/CT uptake variables,CAF-related indicators,and immune indicators.Results FAPI uptake variable SUV_(mean) had statistically significant correlation with FAP(r=0.65,P=0.020),α-SMA(r=0.54,P=0.014),PDGFRα/β(r=0.72,P=0.001),S100A4(r=0.76,P<0.001)and Vimentin(r=0.63,P=0.003).The FAPI uptake variables SUV_(max) and TLF also had significantly positive correlations with the expression of CAF-associated proteins(FAP,α-SMA,PDGFRα/β,S100A4,and Vimentin).FAPI uptake variable SUV_(mean) was negatively correlated with CD8(r=-0.48,P=0.032)and CD163(r=-0.55,P=0.012).FAPI uptake variables SUV_(max),MTV,and TLF also had low negative correlations with CD8and CD163.Conclusions ^(18)F-FAPI-04PET/CT uptake variables can visualize the expression of CAF-related proteins and immune markers,which may provide some guiding significance in clinically identifying high-risk patients for early intensive treatment and identifying patients receiving immunotherapy.Compared with ^(18)F-FDG-PET/CT,^(18)F-FAPI-04-PET/CT had better liver tumor-background ratio,clearer identification of liver metastasis,and higher specificity in detecting lymph node metastasis.