Research progress for the clinical application of radionuclide labeling fibroblast activation protein inhibitor in the diagnosis and treatment of liver cancer
-
摘要:
肝癌在全球具有较高的发病率和死亡率，传统形态学影像可为其诊疗提供重要的疾病解剖信息，而结合PET显像所反映的功能信息可进一步提升肿瘤的诊断准确度并辅助治疗决策。成纤维细胞激活蛋白（fibroblast activation protein, FAP）是肿瘤相关成纤维细胞的标志性蛋白，在多种上皮来源的恶性肿瘤中高表达，是肿瘤诊治的重要靶点。相较于常规应用的18F-氟代脱氧葡萄糖PET显像，FAP抑制剂PET显像具有图像对比度高和不受血糖影响等优势。近年来，靶向FAP的多种放射性药物在不同肝癌类型的诊断、分期及靶向治疗等方面得到了持续拓展，本文对其相关应用进展进行综述。
-
关键词:
- 肝癌 /
- 成纤维细胞激活蛋白抑制剂 /
- 18F-氟代脱氧葡萄糖 /
- 正电子发射断层显像术 /
- 体层摄影术 /
- X线计算机
Abstract:Liver cancer has high morbidity and mortality worldwide. Traditional morphological imaging can offer crucial anatomical information for the diagnosis and treatment of liver cancer, and when combined with the functional data shown by PET imaging, the diagnostic accuracy of tumors can be further improved and assisted in treatment selection. Fibroblast activation protein (FAP), a signature protein of cancer-associated fibroblasts, is highly expressed in a variety of malignant tumors of epithelial origin and is an important target for tumor diagnosis and treatment. Compared with routinely applied 18F-fluorodeoxyglucose (FDG) PET imaging, FAP inhibitor (FAPI) PET imaging has the advantages of high image contrast and independence from blood glucose. In recent years, a variety of radiopharmaceuticals targeting FAP have been continuously expanded in the diagnosis, staging and targeted therapy of different liver cancer types, and the progress of their related applications is reviewed in this paper.
-
肝癌分为原发性和转移性，原发性肝癌包括肝细胞癌（hepatocellular carcinoma, HCC）、肝内胆管癌（intrahepatic cholangiocarcinoma, ICC）以及特殊类型肝癌[1]。肝癌发病隐匿，多数患者在确诊时已是中晚期，预后较差，因此早期诊断及分期对改善患者预后至关重要。超声影像检查方便易得，但受操作者主观因素影响较大。增强CT和MRI是肝肿瘤诊断和鉴别诊断的重要手段，两者对小肝癌（＜3 cm）的诊断灵敏度均高于80%[2]。然而，增强CT增加了患者所受辐射及不良反应，而MRI扫描时间长、易出现运动伪影，降低了病灶诊断精度。影像引导下的穿刺活检有助于明确诊断，但有创，且难以充分反映肿瘤的异质性。
PET显像可无创获取功能影像信息，弥补了传统形态学影像的缺陷。18F-氟代脱氧葡萄糖（18F-fluorodeoxyglucose，18F-FDG）是应用最广的PET示踪剂，但对HCC和ICC病灶的探测价值有限。18F-FDG PET对HCC的探测灵敏度为50%～70%，与CT相当[3]，其原因在于正常肝实质与高分化HCC的18F-FDG摄取程度相近，对比不明显。ICC则低表达己糖激酶2，18F-FDG摄取程度通常变化较大[4-5]。荟萃分析[6]结果显示，尽管18F-FDG PET诊断ICC原发灶的灵敏度高达94.2%，但特异度仅为68.3%。
成纤维细胞激活蛋白（fibroblast activation protein，FAP）是肿瘤相关成纤维细胞（cancer-associated fibroblasts，CAFs）的标志性蛋白，可促进肿瘤细胞的侵袭和迁移[7-8]。FAP在正常组织中低表达，而在肝癌、食管癌及胃癌等伴有显著纤维增生反应的恶性肿瘤中高表达，是相关肿瘤诊治的重要靶点[9-11]。目前，已有数十种放射性核素标记的FAP抑制剂（FAP inhibitor，FAPI）衍生物应用于恶性肿瘤诊疗[12-13]，其中68Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA）-FAPI-04（68Ga-FAPI-04）能产生较好的图像质量，临床应用最为广泛[14-15]。与18F-FDG显像相比，FAPI显像凭借图像对比度高和不受血糖影响等优势在肝癌的诊疗应用中得到不断拓展，本文对相关进展综述如下。
1. FAPI显像在肝癌诊断中的应用进展
1.1 HCC
HCC是全球第六大常见癌症和第三大癌症的死亡原因，占原发性肝癌的75%～85%[1]。HCC常继发于肝纤维化或肝硬化，伴有活化的成纤维细胞积累[16]，因而FAPI显像具有应用优势。FAPI PET/CT显像在原发性肝癌中的主要临床研究见表1。
表 1 FAPI PET/CT在原发性肝癌中的主要临床研究Table 1. Major clinical studies of FAPI PET/CT in primary liver cancerStudy Study design Modalities studied Criteria for final diagnosis Number of patients Tumor type Radiopharmaceutical Guo et al, 2021[5] Retrospective FAPI/FDG PET/CT、CECT、MRI Histopathology, radiography and clinical examinations 34 HCC and ICC 68Ga-FAPI-04 Shi et al, 2021[17] Prospective FAPI PET/CT、CECT/MRI Histopathology 17 HCC, ICC and liver metastases 68Ga-FAPI-04 Shi et al, 2021[18] Prospective FAPI/FDG PET/CT Histopathology, radiography and clinical examinations 20 HCC and ICC 68Ga-FAPI-04 Wang et al, 2021[19] Retrospective FAPI/FDG PET/CT Histopathology and radiography 25 HCC 68Ga-FAPI-04 Zhang et al, 2023[20] Prospective FAPI/FDG PET/CT Histopathology, radiography and clinical examinations 37 HCC, ICC and liver metastases 18F-FAPI Siripongsatian et al, 2022[21] Retrospective FAPI/FDG PET/CT Histopathology and radiography 27 HCC and cholangiocarcinoma 68Ga-FAPI-46 Pabst et al, 2023[22] Prospective FAPI/FDG PET/CT、CECT Histopathology, radiography and clinical examinations 10 Cholangiocarcinoma 68Ga-FAPI-46 Li et al, 2023[23] Prospective FAPI/FDG PET/CT、CT/MRI Histopathology, radiography and clinical examinations 47 Cholangiocarcinoma and gallbladder cancer 68Ga-FAPI-04 FAPI: fibroblast activation protein inhibitor; FDG: fluorodeoxyglucose; PET/CT: positron emission tomography/computed tomography; CECT: contrast-enhanced computed tomography; MRI: magnetic resonance imaging; HCC: hepatocellular carcinoma; ICC: intrahepatic cholangiocarcinoma. 基于68Ga-FAPI-04探针，Shi等[17]进行FAPI PET显像初步研究结果显示，28个肝内恶性病灶均示踪剂高摄取（平均SUVmax为8.4）。免疫组化进一步揭示，活检的8个HCC病灶中6个FAP显著表达，表明FAPI PET成像技术可有效反映HCC病变中FAP的表达水平。后续研究[18]发现，68Ga-FAPI显像对于不同分化程度HCC病灶的检出率均高于18F-FDG显像，其总体探测灵敏度为100%，显著优于18F-FDG显像（43.8%），这一优势在Wang等[19]研究中得到进一步验证。Guo等[5]基于20例HCC患者进一步探讨68Ga-FAPI PET/CT显像的病灶探测优势结果显示，68Ga-FAPI显像对HCC原发灶的探测灵敏度虽明显高于18F-FDG显像（94% vs 69%），但与增强CT（94%）和MRI（100%）相当。然而，2例HCC患者通过68Ga-FAPI显像检出更多病灶，改变了分期及后续治疗方案，提示68Ga-FAPI显像在改善分期及优化治疗决策上的潜在优势。
另有多项研究围绕优化的探针开展了针对肝癌的临床应用探索。Zhang等[20]研究发现，Al18F-1,4,7-三氮杂环壬烷-1,4,7-三乙酸（1,4,7-triazacyclononane-1,4,7-triacetic acid, NOTA）-FAPI显像对18F-FDG显像为阴性的HCC病灶的探测灵敏度高达97.0%（32/33），进一步验证了FAPI显像在改善分期及优化治疗决策上的应用优势。然而，Siripongsatian等[21]基于14例HCC患者的对比研究发现，尽管68Ga-DOTA-FAPI-46（通过甲基化氮取代FAPI-04喹啉6号位上的氧合成，简称68Ga-FAPI-46）显像探测HCC病灶较18F-FDG显像灵敏度更高（100% vs 71%），仍有2个18F-FDG高摄取骨转移灶在68Ga-FAPI-46显像上未检出，表明肿瘤的FAP表达存在异质性，而多探针联合可反映更为全面的肿瘤生物学特性。在动态显像方面，Geist等[24]基于8例疑似肝癌患者（4例HCC）的研究数据表明，基于动力学模型获取的68Ga-FAPI-04动力学参数有助于从肝癌和正常肝实质中识别出HCC，为肝癌的鉴别诊断提供了新的评估视角。
总之，FAPI PET/CT显像对HCC具有较高的探测灵敏度，在其鉴别诊断、分期判断以及治疗决策优化等方面较常规影像学检查具有重要补充价值。
1.2 ICC
ICC是一种胆管上皮细胞起源的原发性胆道癌，占原发性肝癌的10%～15%[25]。由于ICC伴有显著的纤维结缔组织增生和FAP高表达，FAPI显像可能有助于表征其肿瘤微环境的标志性特征。Guo等[5]对34例疑似肝癌患者（20例HCC，12例ICC）行68Ga-FAPI-04与18F-FDG PET对比显像发现，ICC病灶的68Ga-FAPI-04摄取显著高于其18F-FDG摄取和HCC病灶的68Ga-FAPI-04摄取，佐证了ICC纤维结缔组织显著增生的特点。
为评估FAPI显像较常规影像学检查的实际增益，Pabst等[22]对10例胆管癌患者（6例ICC）行68Ga-FAPI-46 PET/CT显像，并与18F-FDG显像和增强CT进行对比分析，结果显示三者虽均检出所有原发灶，但对于转移淋巴结和远处转移灶，68Ga-FAPI-46显像（均为100%）的探测灵敏度均优于18F-FDG显像（90.9%和66.7%）和增强CT（27.3%和33.3%）。然而，受限于小样本量以及晚期患者居多，该研究未能进一步观察到FAPI显像对于治疗决策的影响。Li等[23]基于更大样本（47例疑似胆道癌患者，包括22例ICC）的对比研究发现，虽然68Ga-FAPI-04显像对于胆道癌原发灶（97.6% vs 85.7%）、转移淋巴结（90.1% vs 87.1%）、远处转移灶（100% vs 83.7%）和ICC原发灶（100% vs 95.5%）等各类病灶的检出率均高于18F-FDG显像，两者提供了一致的肿瘤分期/再分期结果，但相较于CT或MRI，68Ga-FAPI-04显像上调了14例患者（9例ICC）的分期/再分期，其中6例患者的治疗方案发生重要改变，为FAPI显像在治疗决策优化方面提供了数据支持。
总之，68Ga-FAPI PET/CT在肿瘤间质显像方面具有高灵敏度，可有效提高ICC病灶检出率并提升诊断及分期准确性，有助于临床诊疗决策优化。
1.3 特殊类型原发性肝癌
目前，FAPI显像在特殊类型原发性肝癌中的应用多为个案报道。Ergül等[26]报道了1例肝脏神经内分泌癌患者的18F-FDG和68Ga-FAPI-04 PET/CT对比显像，尽管肿瘤的Ki-67增殖指数高达80%，病灶的18F-FDG摄取仍低于68Ga-FAPI-04摄取（SUVmax：10.5 vs 15.6），提示FAPI显像可能有助于检出18F-FDG低摄取的肝脏神经内分泌癌。Pang等[27]报道了1例原发性肝黏膜相关淋巴组织淋巴瘤患者的对比显像结果。尽管病灶的68Ga-FAPI-04摄取略低于18F-FDG摄取（SUVmax：2.5 vs 2.8），然而前者提供了更高的肿瘤/本底比值（1.6 vs 0.7），这也为非特异性18F-FDG摄取的淋巴瘤患者的肝脏受累范围评估提供了新的视角。
1.4 转移性肝癌
肝脏是多数实体恶性肿瘤转移的主要部位，然而18F-FDG PET/CT在探测最大径＜1.0 cm且糖代谢程度接近正常肝实质的肝转移灶方面具有挑战[28]。由于正常肝实质的FAPI摄取显著低于FDG摄取，FAPI显像有助于转移灶检出。
在病灶探测方面，Şahin等[29]基于31例肿瘤患者（98个肝转移灶）的研究显示，68Ga-FAPI-04显像探测肝转移灶的灵敏度显著优于18F-FDG显像（96.8% vs 80.2%），与Kaplan等[30]研究结果一致。然而，尽管68Ga-FAPI-04显像额外检出了7例18F-FDG显像阴性的肝转移患者，仍有1例患者的3个肝转移灶仅被18F-FDG显像检出，强调了两者联合以形成信息互补的必要性。
病灶探测的高灵敏度有利于精准判断肿瘤分期，进而优化其治疗决策。Koerber等[31]对22例下消化道肿瘤患者行68Ga-FAPI PET/CT显像（16例为68Ga-FAPI-04显像，6例为68Ga-FAPI-46显像），结果显示肝转移灶在所有转移灶中具有最高的示踪剂摄取值，平均SUVmax为9.1。总体上，68Ga-FAPI显像改变了50%（3/6）未治疗患者的肿瘤分期和47%（7/15）已转移患者的病灶检出数，调整了81%（17/21）患者的治疗方案，其中19%（4/21）为完全改变，29%（6/21）为放疗靶区勾画的调整。
总之，68Ga-FAPI PET/CT结合常规影像学检查可提升肝转移患者的肿瘤分期/再分期准确性，进而指导个性化治疗决策的制定。
2. FAPI靶向肝癌治疗的应用进展
凭借较高的肿瘤摄取和肿瘤/本底比值，FAP被视为核素靶向治疗中极具潜力的泛癌靶点。目前，针对肝癌的FAPI靶向核素治疗研究均基于高异质性队列，且仅初步评估了治疗的可行性和安全性[32-34]。其中，Kuyumcu等[32]对4例晚期恶性肿瘤患者（2例伴肝转移）行177Lu-DOTA-FAPI-04放射性治疗，给药当天至第10天均未见不良反应或病情恶化。然而，肿瘤病灶的平均吸收剂量较低（骨转移灶最高）。为进一步增强探针的肿瘤摄取并延长滞留时间，Yadav等[35]通过多聚化策略合成了177Lu-1,4,7,10-四氮杂环十二烷-1-谷氨酸-4,7,10-三乙酸（1,4,7,10-tetraazacyclododecane-1-glutamic acid-4,7,10-triacetic acid, DOTAGA）.Glu.(FAPI)2和177Lu-DOTAGA.(SA.FAPI)2（SA为方酸），并对19例转移性乳腺癌患者（5例伴肝转移）进行靶向治疗，结果显示95%（18/19）的患者实现疾病控制，临床客观缓解率为84%，且未观察到治疗相关的严重不良反应。目前，针对特定肝癌类型的FAPI靶向核素治疗研究仍非常有限，核素的选择、剂量考虑、给药时间、长期安全性和可能的不良反应等均需更大规模的前瞻性临床试验评估。
3. 机遇与挑战
肝纤维化及胆道炎症等非肿瘤性疾病亦存在FAPI高摄取，易导致假阳性诊断。而对于肝癌手术或放化疗后的FAPI显像评估，目前仍无合适的显像时间窗以区分残余癌灶/复发和炎性/纤维化活动。此外，现有研究所采用的探针类型、注射剂量、图像采集/重建方案和病变诊断标准均存在较大差异，未来还需要更多标准化的系列研究以充分挖掘FAPI肝脏显像的优势与不足。在核素治疗方面，现有研究仅针对多癌种队列初步评估了其可行性和安全性且疗效多为混合反应，缺乏基于高同质性肝癌队列的可靠数据。正常组织的生理性摄取也使得治疗剂量、治疗效果及不良反应等亟待全面评估。
综上所述，FAPI靶向肝癌诊疗具有良好的临床应用前景：在诊断及分期方面，FAPI显像可通过提高病灶检出率以准确调整部分患者的疾病分期，有助于诊疗决策优化；在核素靶向治疗方面，现有临床数据表明晚期癌症患者接受治疗后有客观获益且不良事件可控。然而，目前针对特定肝癌类型的研究尚未达到足够的深度和广度。此外，非肿瘤性FAPI摄取也对影像标准的解读范式提出了更高要求。总体来说，基于FAPI的成像技术可提供病变病理生理学变化的多维信息，是18F-FDG显像以及传统形态学影像的有效补充。随着探针的持续优化，未来仍需要更多基于同质患者群体的前瞻性研究以析清其在不同临床场景下的优势与局限，从而证实其在肝癌诊治中的确切效能。
伦理声明 无。
利益冲突 所有作者声明不存在利益冲突。
作者贡献 何依波：文献检索、总结及撰稿；石洪成：主题选定及文章审核。
-
表 1 FAPI PET/CT在原发性肝癌中的主要临床研究
Table 1 Major clinical studies of FAPI PET/CT in primary liver cancer
Study Study design Modalities studied Criteria for final diagnosis Number of patients Tumor type Radiopharmaceutical Guo et al, 2021[5] Retrospective FAPI/FDG PET/CT、CECT、MRI Histopathology, radiography and clinical examinations 34 HCC and ICC 68Ga-FAPI-04 Shi et al, 2021[17] Prospective FAPI PET/CT、CECT/MRI Histopathology 17 HCC, ICC and liver metastases 68Ga-FAPI-04 Shi et al, 2021[18] Prospective FAPI/FDG PET/CT Histopathology, radiography and clinical examinations 20 HCC and ICC 68Ga-FAPI-04 Wang et al, 2021[19] Retrospective FAPI/FDG PET/CT Histopathology and radiography 25 HCC 68Ga-FAPI-04 Zhang et al, 2023[20] Prospective FAPI/FDG PET/CT Histopathology, radiography and clinical examinations 37 HCC, ICC and liver metastases 18F-FAPI Siripongsatian et al, 2022[21] Retrospective FAPI/FDG PET/CT Histopathology and radiography 27 HCC and cholangiocarcinoma 68Ga-FAPI-46 Pabst et al, 2023[22] Prospective FAPI/FDG PET/CT、CECT Histopathology, radiography and clinical examinations 10 Cholangiocarcinoma 68Ga-FAPI-46 Li et al, 2023[23] Prospective FAPI/FDG PET/CT、CT/MRI Histopathology, radiography and clinical examinations 47 Cholangiocarcinoma and gallbladder cancer 68Ga-FAPI-04 FAPI: fibroblast activation protein inhibitor; FDG: fluorodeoxyglucose; PET/CT: positron emission tomography/computed tomography; CECT: contrast-enhanced computed tomography; MRI: magnetic resonance imaging; HCC: hepatocellular carcinoma; ICC: intrahepatic cholangiocarcinoma. 
下载: 导出CSV
-
[1] SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660
[2] HSIAO C Y, CHEN P D, HUANG K W. A prospective assessment of the diagnostic value of contrast-enhanced ultrasound, dynamic computed tomography and magnetic resonance imaging for patients with small liver tumors[J]. J Clin Med, 2019, 8(9): 1353. DOI: 10.3390/jcm8091353
[3] TROJAN J, SCHROEDER O, RAEDLE J, et al. Fluorine-18 FDG positron emission tomography for imaging of hepatocellular carcinoma[J]. Am J Gastroenterol, 1999, 94(11): 3314-3319. DOI: 10.1111/j.1572-0241.1999.01544.x
[4] PAUDYAL B, ORIUCHI N, PAUDYAL P, et al. Clinicopathological presentation of varying 18F-FDG uptake and expression of glucose transporter 1 and hexokinase Ⅱ in cases of hepatocellular carcinoma and cholangiocellular carcinoma[J]. Ann Nucl Med, 2008, 22(1): 83-86. DOI: 10.1007/s12149-007-0076-1
[5] GUO W, PANG Y Z, YAO L L, et al. Imaging fibroblast activation protein in liver cancer: a single-center post hoc retrospective analysis to compare[68Ga]Ga-FAPI-04 PET/CT versus MRI and[18F]-FDG PET/CT[J]. Eur J Nucl Med Mol Imaging, 2021, 48(5): 1604-1617. DOI: 10.1007/s00259-020-05095-0
[6] LAMARCA A, BARRIUSO J, CHANDER A, et al. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) for patients with biliary tract cancer: systematic review and meta-analysis[J]. J Hepatol, 2019, 71(1): 115-129. DOI: 10.1016/j.jhep.2019.01.038
[7] MORI Y, DENDL K, CARDINALE J, et al. FAPI PET: fibroblast activation protein inhibitor use in oncologic and nononcologic disease[J]. Radiology, 2023, 306(2): e220749. DOI: 10.1148/radiol.220749
[8] 张馨月, 韩 巍, 吕哲昊, 等. FAPI PET/CT在肝脏恶性肿瘤诊断中的研究进展[J]. 中华肝脏病杂志, 2023, 31(6): 664-667. DOI: 10.3760/cma.j.cn501113-20230313-00110 ZHANG X Y, HAN W, LYU Z H, et al. Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors[J]. Chin J Hepatol, 2023, 31(6): 664-667. DOI: 10.3760/cma.j.cn501113-20230313-00110
[9] GARIN-CHESA P, OLD L J, RETTIG W J. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers[J]. Proc Natl Acad Sci USA, 1990, 87(18): 7235-7239. DOI: 10.1073/pnas.87.18.7235
[10] RETTIG W J, SU S L, FORTUNATO S R, et al. Fibroblast activation protein: purification, epitope mapping and induction by growth factors[J]. Int J Cancer, 1994, 58(3): 385-392. DOI: 10.1002/ijc.2910580314
[11] SIVEKE J T. Fibroblast-activating protein: targeting the roots of the tumor microenvironment[J]. J Nucl Med, 2018, 59(9): 1412-1414. DOI: 10.2967/jnumed.118.214361
[12] VAN DEN HOVEN A F, KEIJSERS R G M, LAM M G E H, et al. Current research topics in FAPI theranostics: a bibliometric analysis[J]. Eur J Nucl Med Mol Imaging, 2023, 50(4): 1014-1027. DOI: 10.1007/s00259-022-06052-9
[13] 宋杨美惠, 李梦婷, 兰晓莉, 等. 靶向成纤维细胞激活蛋白放射性药物在恶性肿瘤诊疗中的研究进展[J]. 药学进展, 2023, 9(5): 337-356. SONG Y M H, LI M T, LAN X L, et al. Research progress of radiopharmaceuticals targeting fibroblast activation protein in the diagnosis and treatment of malignant tumors[J]. Prog Pharm Sci, 2023, 9(5): 337-356.
[14] KRATOCHWIL C, FLECHSIG P, LINDNER T, et al. 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer[J]. J Nucl Med, 2019, 60(6): 801-805. DOI: 10.2967/jnumed.119.227967
[15] 王 彬, 赵 妍, 陈 旸, 等. 68Ga-FAPI PET/CT在胃及结直肠肿瘤诊疗中的临床应用进展[J]. 国际放射医学核医学杂志, 2023, 47(1): 39-44. DOI: 10.3760/cma.j.cn121381-202205016-00259 WANG B, ZHAO Y, CHEN Y, et al. Clinical application and progress of 68Ga-FAPI PET/CT in the diagnosis and treatments of gastric and colorectal tumors[J]. Int J Radiat Med Nucl Med, 2023, 47(1): 39-44. DOI: 10.3760/cma.j.cn121381-202205016-00259
[16] XU H X, ZHAO J, LI J P, et al. Cancer associated fibroblast-derived CCL5 promotes hepatocellular carcinoma metastasis through activating HIF1α/ZEB1 axis[J]. Cell Death Dis, 2022, 13(5): 478. DOI: 10.1038/s41419-022-04935-1
[17] SHI X M, XING H Q, YANG X B, et al. Fibroblast imaging of hepatic carcinoma with 68Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules[J]. Eur J Nucl Med Mol Imaging, 2021, 48(1): 196-203. DOI: 10.1007/s00259-020-04882-z
[18] SHI X M, XING H Q, YANG X B, et al. Comparison of PET imaging of activated fibroblasts and 18F-FDG for diagnosis of primary hepatic tumours: a prospective pilot study[J]. Eur J Nucl Med Mol Imaging, 2021, 48(5): 1593-1603. DOI: 10.1007/s00259-020-05070-9
[19] WANG H, ZHU W W, REN S H, et al. 68Ga-FAPI-04 versus 18F-FDG PET/CT in the detection of hepatocellular carcinoma[J]. Front Oncol, 2021, 11: 693640. DOI: 10.3389/fonc.2021.693640
[20] ZHANG J, HE Q, JIANG S Q, et al. [18F]FAPI PET/CT in the evaluation of focal liver lesions with[18F]FDG non-avidity[J]. Eur J Nucl Med Mol Imaging, 2023, 50(3): 937-950. DOI: 10.1007/s00259-022-06022-1
[21] SIRIPONGSATIAN D, PROMTEANGTRONG C, KUNAWUDHI A, et al. Comparisons of quantitative parameters of Ga-68-labelled fibroblast activating protein inhibitor (FAPI) PET/CT and[18F]F-FDG PET/CT in patients with liver malignancies[J]. Mol Imaging Biol, 2022, 24(5): 818-829. DOI: 10.1007/s11307-022-01732-2
[22] PABST K M, TRAJKOVIC-ARSIC M, CHEUNG P F Y, et al. Superior tumor detection for 68Ga-FAPI-46 versus 18F-FDG PET/CT and conventional CT in patients with cholangiocarcinoma[J]. J Nucl Med, 2023, 64(7): 1049-1055. DOI: 10.2967/jnumed.122.265215
[23] LI J H, XU K, GUO D L, et al. Correction to: Clinical prospective study of Gallium 68 (68Ga)-labeled fibroblast-activation protein inhibitor PET/CT in the diagnosis of biliary tract carcinoma[J]. Eur J Nucl Med Mol Imaging, 2023, 50(7): 2230. DOI: 10.1007/s00259-023-06188-2
[24] GEIST B K, XING H Q, WANG J N, et al. A methodological investigation of healthy tissue, hepatocellular carcinoma, and other lesions with dynamic 68Ga-FAPI-04 PET/CT imaging[J]. EJNMMI Phys, 2021, 8(1): 8. DOI: 10.1186/s40658-021-00353-y
[25] SQUADRONI M, TONDULLI L, GATTA G, et al. Cholangiocarcinoma[J]. Crit Rev Oncol Hematol, 2017, 116: 11-31. DOI: 10.1016/j.critrevonc.2016.11.012
[26] ERGÜL N, YILMAZ B, CIN M, et al. 68Ga-DOTA-FAPI-04 PET/CT in neuroendocrine carcinoma of the liver with elevated AFP level: comparison with 18F-FDG PET/CT[J]. Clin Nucl Med, 2022, 47(1): e29-e31. DOI: 10.1097/RLU.0000000000003811
[27] PANG Y Z, ZHAO L, SHANG Q H, et al. 18F-FDG versus 68Ga-FAPI PET/CT in visualizing primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue[J]. Clin Nucl Med, 2022, 47(4): 375-377. DOI: 10.1097/RLU.0000000000003948
[28] 吕清湖, 林端瑜, 刘道佳, 等. 胃肠道间质瘤肝转移灶的18F-FDG PET/CT显像特点[J]. 中华核医学与分子影像杂志, 2021, 41(2): 71-75. DOI: 10.3760/cma.j.cn321828-20191230-00301 LÜ Q H, LIN D Y, LIU D J, et al. 18F-FDG PET/CT imaging features of hepatic metastases in gastrointestinal stromal tumors[J]. Chin J Nucl Med Mol Imag, 2021, 41(2): 71-75. DOI: 10.3760/cma.j.cn321828-20191230-00301
[29] ŞAHIN E, ELBOĞA U, ÇELEN Y Z, et al. Comparison of 68Ga-DOTA-FAPI and 18FDG PET/CT imaging modalities in the detection of liver metastases in patients with gastrointestinal system cancer[J]. Eur J Radiol, 2021, 142: 109867. DOI: 10.1016/j.ejrad.2021.109867
[30] KAPLAN İ, KEPENEK F, GÜZEL Y, et al. The role of 68Ga FAPI-04 and 18F-FDG PET/CT in detecting liver metastases in different types of cancer[J]. Nuklearmedizin, 2023, 62(4): 252-259. DOI: 10.1055/a-2127-7699
[31] KOERBER S A, STAUDINGER F, KRATOCHWIL C, et al. The role of 68Ga-FAPI PET/CT for patients with malignancies of the lower gastrointestinal tract: first clinical experience[J]. J Nucl Med, 2020, 61(9): 1331-1336. DOI: 10.2967/jnumed.119.237016
[32] KUYUMCU S, KOVAN B, SANLI Y, et al. Safety of fibroblast activation protein-targeted radionuclide therapy by a low-dose dosimetric approach using 177Lu-FAPI04[J]. Clin Nucl Med, 2021, 46(8): 641-646. DOI: 10.1097/RLU.0000000000003667
[33] BAUM R P, SCHUCHARDT C, SINGH A, et al. Feasibility, biodistribution, and preliminary dosimetry in peptide-targeted radionuclide therapy of diverse adenocarcinomas using 177Lu-FAP-2286: first-in-humans results[J]. J Nucl Med, 2022, 63(3): 415-423. DOI: 10.2967/jnumed.120.259192
[34] FERDINANDUS J, COSTA P F, KESSLER L, et al. Initial clinical experience with 90Y-FAPI-46 radioligand therapy for advanced-stage solid tumors: a case series of 9 patients[J]. J Nucl Med, 2022, 63(5): 727-734.
[35] YADAV M P, BALLAL S, MARTIN M, et al. Therapeutic potential of[177Lu]Lu-DOTAGA-FAPi dimers in metastatic breast cancer patients with limited treatment options: efficacy and safety assessment[J]. Eur J Nucl Med Mol Imaging, 2024, 51(3): 805-819. DOI: 10.1007/s00259-023-06482-z
计量
- 文章访问数: 108
- HTML全文浏览量: 21
- PDF下载量: 12
