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Article(id=1194617493667946689, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1631.2024.0708, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1702051200000, receivedDateStr=2023-12-09, revisedDate=null, revisedDateStr=null, acceptedDate=1715356800000, acceptedDateStr=2024-05-11, onlineDate=1762748605410, onlineDateStr=2025-11-10, pubDate=1740672000000, pubDateStr=2025-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762748605410, onlineIssueDateStr=2025-11-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762748605410, creator=13701087609, updateTime=1762748605410, updator=13701087609, issue=Issue{id=1194617490446721194, tenantId=1146029695717560320, journalId=1189873630562394117, year='2025', volume='50', issue='2', pageStart='123', pageEnd='244', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1762748604641, creator=13701087609, updateTime=1762749162199, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1194619829073191185, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1194619829073191186, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=154, endPage=161, ext={EN=ArticleExt(id=1194617493965742277, articleId=1194617493667946689, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Clinical diagnosis value of 18F-fibroblast-activation protein inhibitor PET/CT in malignant tumors with low 18F-fluorodeoxyglucose uptake, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To evaluate the clinical value of 18F-fibroblast-activation protein inhibitor (18F-FAPI) PET/CT in malignant tumors exhibiting low uptake of 18F-fluorodeoxyglucose (18F-FDG). Methods We prospectively analyzed 62 patients with malignant tumors and low 18F-FDG uptake who underwent 18F-FAPI PET/CT in the Affiliated Cancer Hospital and Institute of Guangzhou Medical University from January 2021 to November 2022. Patient demographics information, clinical and radiological data were collected. Tumor lesions were categorized based on 18F-FAPI and 18F-FDG uptake relative to surrounding tissues into low-, moderate-, and high-uptake, with high uptake indicating positivity. The number and tracer uptake levels of primary tumors and metastatic lesions visualized by both 18F-FDG and 18F-FAPI were recorded and compared. Results Of the 62 primary tumors, 18(29.0%) showed low-uptake and 44 (71.0%) moderate-uptake on 18F-FDG PET, while 1(1.6%), 6(9.7%), and 55(88.7%) showed low, moderate, and high uptake on 18F-FAPI, respectively. The maximum standardized uptake value (SUVmax) for primary tumors was significantly higher with 18F-FAPI than with 18F-FDG (7.5±5.6 vs. 3.9±2.1, P<0.01). The number of positive lymph node foci revealed by 18F-FAPI was noticeably higher than that by 18F-FDG (77 vs. 38, P<0.01). A total of 16 distant organ metastases were identified, with 11(68.8%) detected by 18F-FDG and 15(93.8%) by 18F-FAPI, showing no significant difference in detection rates (P>0.05). Conclusions 18F-FAPI PET/CT effectively visualizes primary and metastatic lesions in malignant tumors with low 18F-FDG uptake, suggesting its potential as a promising radiotracer for such malignancies.

, correspAuthors=Wei Li, authorNote=null, correspAuthorsNote=
E-mail:
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目的 探讨18F标记的成纤维细胞活化蛋白抑制剂(18F-FAPI)PET/CT对18F-氟代脱氧葡萄糖(18F-FDG)摄取偏低的恶性肿瘤的临床诊断价值。方法 前瞻性选取2021年1月－2022年11月在广州医科大学附属肿瘤医院确诊并接受18F-FAPI PET/CT检查的62例18F-FDG摄取偏低的恶性肿瘤患者。收集所有患者的一般信息、临床和影像资料。参照肿瘤邻近组织对18F-FDG和18F-FAPI的摄取水平，将肿瘤病灶分为高摄取、中摄取与低摄取，其中高摄取病灶设为阳性。记录并比较18F-FDG与18F-FAPI显示的肿瘤原发灶、转移灶数量及其摄取水平。结果 62例原发恶性肿瘤对18F-FDG低摄取18例(29.0%)、中摄取44例(71.0%)，而对18F-FAPI低摄取1例(1.6%)、中摄取6例(9.7%)、高摄取55例(88.7%)。原发肿瘤18F-FAPI的最大标准摄取值(SUVmax)明显高于18F-FDG(7.5±5.6 vs. 3.9±2.1，P<0.001)。18F-FAPI PET检出的阳性淋巴结数明显多于18F-FDG PET(77个 vs. 38个，P<0.01)。共检出16个远处转移灶，其中18F-FDG PET/CT检出11个(68.8%)，18F-FAPI PET/CT检出15个(93.8%)，两种示踪剂的检出率比较差异无统计学意义(P>0.05)。结论 对于18F-FDG摄取偏低的恶性肿瘤，18F-FAPI PET/CT可较好地显示肿瘤原发灶和转移灶。18F-FAPI可作为一种较有前景的放射性示踪剂，尤其适用于18F-FDG摄取偏低的恶性肿瘤。

, correspAuthors=李伟, authorNote=null, correspAuthorsNote=
李伟，E-mail：
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梁志盈，硕士研究生，主要从事肺肿瘤分子影像诊断方面的研究

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梁志盈，硕士研究生，主要从事肺肿瘤分子影像诊断方面的研究

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梁志盈，硕士研究生，主要从事肺肿瘤分子影像诊断方面的研究

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J Nucl Med, 2023, 64(4): 625-631., articleTitle=Response prediction using 18F-FAPI-04 PET/CT in patients with esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy, refAbstract=null), Reference(id=1194646644487590848, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, doi=null, pmid=null, pmcid=null, year=2022, volume=49, issue=8, pageStart=2833, pageEnd=2843, url=null, language=null, rfNumber=[25], rfOrder=24, authorNames=Hu K, Wang L, Wu H, journalName=Eur J Nucl Med Mol Imaging, refType=null, unstructuredReference=Hu K, Wang L, Wu H, et al. [18F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [68Ga]Ga-FAPI-04[J]. Eur J Nucl Med Mol Imaging, 2022, 49(8): 2833-2843., articleTitle=[18F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [68Ga]Ga-FAPI-04, refAbstract=null), Reference(id=1194646644563088321, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, doi=null, pmid=null, pmcid=null, year=2023, volume=50, issue=3, pageStart=937, pageEnd=950, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=Zhang J, He Q, Jiang S, journalName=Eur J Nucl Med Mol Imaging, refType=null, unstructuredReference=Zhang J, He Q, Jiang S, 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., articleTitle=[18F]FAPI PET/CT in the evaluation of focal liver lesions with [18F]FDG non-avidity, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1194646637294359409, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, xref=null, ext=[AuthorCompanyExt(id=1194646637302748018, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, companyId=1194646637294359409, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Nuclear Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, China), AuthorCompanyExt(id=1194646637311136627, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, companyId=1194646637294359409, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=广州医科大学附属肿瘤医院核医学科，广东广州 510095)])], figs=[ArticleFig(id=1194646640595276695, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Fig.1, caption=18F-FDG and 18F-FAPI PET/CT images of 3 cases with hepatocellular carcinoma, figureFileSmall=JJKAHwbaFLZoppNq6qi0Eg==, figureFileBig=WbBMsVCxNHhMSarkDN4dgA==, tableContent=null), ArticleFig(id=1194646640662385560, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=图1, caption=3例肝细胞癌患者的18F-FDG和18F-FAPI PET/CT成像

CT平扫显示肝低密度肿块；CT增强扫描显示肿块不均匀强化；18F-FDG图像显示这些肿块为中摄取；在18F-FAPI图像上，病例1为低摄取，病例2为中摄取，病例3为高摄取

, figureFileSmall=JJKAHwbaFLZoppNq6qi0Eg==, figureFileBig=WbBMsVCxNHhMSarkDN4dgA==, tableContent=null), ArticleFig(id=1194646640754660249, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Fig.2, caption=18F-FDG and 18F-FAPI PET/CT images of a case of gastric adenocarcinoma with multiple metastases, figureFileSmall=QGM+8tils0iA4LkXKKhPkA==, figureFileBig=BN7/ABgMrRuIoYCaLqCCVA==, tableContent=null), ArticleFig(id=1194646640830157722, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=图2, caption=1例胃腺癌合并多发性转移的18F-FDG和18F-FAPI PET/CT成像

A－D. 原发灶位于胃窦壁上的结节，C. 18F-FDG呈低摄取，D. 18F-FAPI呈高摄取；E－H. 胰尾转移灶对18F-FDG呈中摄取(G)，对18F-FAPI呈高摄取(H)；I－K. 纵隔肿大淋巴结对18F-FDG呈中摄取(J)，对18F-FAPI呈高摄取(K)；L－N. 左侧顶骨转移灶对18F-FDG呈低摄取(M)，对18F-FAPI呈高摄取(N)；O. 18F-FDG最大密度投影未见明显阳性病灶；P. 而18F-FAPI MIP显示多发阳性病灶

, figureFileSmall=QGM+8tils0iA4LkXKKhPkA==, figureFileBig=BN7/ABgMrRuIoYCaLqCCVA==, tableContent=null), ArticleFig(id=1194646640897266587, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Fig.3, caption=18F-FDG and 18F-FAPI PET/CT images of a case of left ductal carcinoma with bone metastasis, figureFileSmall=K/hRDACR1FeL94vV7UkvUg==, figureFileBig=ZvUMxrxKLUHujgo/8tmdXA==, tableContent=null), ArticleFig(id=1194646640960181148, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=图3, caption=1例左乳导管癌合并骨转移的18F-FDG和18F-FAPI PET/CT成像

A、H. CT显示左乳轻度增厚；B、C. 18F-FDG为中摄取；I、J. 18F-FAPI为高摄取；D、K. CT显示第10胸椎溶骨性病变；E、F. 18F-FDG为中摄取；L、M. 18F-FAPI为高摄取；G. 18F-FDG 最大密度投影未见明显阳性病变；N. 18F-FAPI 最大密度投影显示左乳及胸椎阳性病变

, figureFileSmall=K/hRDACR1FeL94vV7UkvUg==, figureFileBig=ZvUMxrxKLUHujgo/8tmdXA==, tableContent=null), ArticleFig(id=1194646641023095709, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Fig.4, caption=18F-FDG and 18F-FAPI PET/CT images of a case of diffuse large B-cell lymphoma in the left brain, figureFileSmall=+bDKGhAShOuEbI5YUUeSUA==, figureFileBig=oPwA1F1ktZRA3Fx67lmePw==, tableContent=null), ArticleFig(id=1194646641086010270, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=图4, caption=1例左脑弥漫性大B细胞淋巴瘤的18F-FDG和18F-FAPI PET/CT成像

肿瘤病灶位于左侧基底节区，18F-FDG的标准摄取值(SUV)为9.1，18F-FAPI的SUV为4.3；但背景组织18F-FDG的SUV为8.7，18F-FAPI的SUV为0.1；A. CT图像呈模糊低密度结节影；B－D. 18F-FDG呈中摄取；E. CT增强扫描呈中度强化；F－H. 18F-FAPI呈高摄取

, figureFileSmall=+bDKGhAShOuEbI5YUUeSUA==, figureFileBig=oPwA1F1ktZRA3Fx67lmePw==, tableContent=null), ArticleFig(id=1194646641153119135, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Fig.5, caption=18F-FDG and 18F-FAPI PET/CT images of two cases of malignant tumor with lung metastasis, figureFileSmall=QKm/ChQrIltcyxOumns1aw==, figureFileBig=Qb8l1ILJMxEEoP3ZezXhiw==, tableContent=null), ArticleFig(id=1194646641216033696, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=图5, caption=2例恶性肿瘤肺转移的18F-FDG和18F-FAPI PET/CT成像

病例1在左肺发现一结节，18F-FDG和18F-FAPI均呈高摄取，诊断为肝细胞癌肺转移，18F-FDG和18F-FAPI的SUV分别为6.3、4.3，可归为FDG≥FAPI；病例2为腹膜广泛增厚，18F-FDG和18F-FAPI均呈高摄取，诊断为卵巢腺癌腹膜转移，18F-FDG和18F-FAPI的SUV分别为7.1、10.5，可归为分为FDG<FAPI

, figureFileSmall=QKm/ChQrIltcyxOumns1aw==, figureFileBig=Qb8l1ILJMxEEoP3ZezXhiw==, tableContent=null), ArticleFig(id=1194646641278948257, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Tab.1, caption=

Results of 18F-FDG and 18F-FAPI PET/CT in 62 patients with primary malignant tumor

, figureFileSmall=null, figureFileBig=null, tableContent=
原发肿瘤例数CT(例)PET
Ⅰ型Ⅱ型Ⅲ型18F-FDG18F-FAPI
低摄取(例)中摄取(例)SUVmax(x±s)低摄取(例)中摄取(例)高摄取(例)SUVmax(x±s)
肝癌27205210174.1±1.013236.2±1.2*
胃癌10442283.5±1.101911.3±5.6*
乳腺癌6222242.7±0.80065.9.±3.1*
口咽癌5032124.0±2.80055.9±3.6*
腹部肿瘤6420333.0±1.20069.4±5.8*
胸部肿瘤3300032.6±0.90123.3±1.3*
肉瘤5401057.5±5.30143.2±2.2*
), ArticleFig(id=1194646641375417251, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=表1, caption=

62例原发恶性肿瘤的18F-FAPI和18F-FDG PET/CT表现

, figureFileSmall=null, figureFileBig=null, tableContent=
原发肿瘤例数CT(例)PET
Ⅰ型Ⅱ型Ⅲ型18F-FDG18F-FAPI
低摄取(例)中摄取(例)SUVmax(x±s)低摄取(例)中摄取(例)高摄取(例)SUVmax(x±s)
肝癌27205210174.1±1.013236.2±1.2*
胃癌10442283.5±1.101911.3±5.6*
乳腺癌6222242.7±0.80065.9.±3.1*
口咽癌5032124.0±2.80055.9±3.6*
腹部肿瘤6420333.0±1.20069.4±5.8*
胸部肿瘤3300032.6±0.90123.3±1.3*
肉瘤5401057.5±5.30143.2±2.2*
), ArticleFig(id=1194646641455109028, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Tab.2, caption=

Positive lymph nodes identified by 18F-FAPI and18F-FDG PET

, figureFileSmall=null, figureFileBig=null, tableContent=
原发肿瘤例数阳性淋巴结(个)
18F-FDG18F-FAPI
合计183877
肝癌4511
胃癌61124
乳腺癌4814
卵巢癌267
肺癌1714
胆囊癌117
), ArticleFig(id=1194646641530606501, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=表2, caption=

18F-FAPI和18F-FDG PET检测的阳性淋巴结

, figureFileSmall=null, figureFileBig=null, tableContent=
原发肿瘤例数阳性淋巴结(个)
18F-FDG18F-FAPI
合计183877
肝癌4511
胃癌61124
乳腺癌4814
卵巢癌267
肺癌1714
胆囊癌117
), ArticleFig(id=1194646641593521062, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=EN, label=Tab.3, caption=

16 distant metastatic lesions identified by 18F-FDG and 18F-FAPI PET/CT

, figureFileSmall=null, figureFileBig=null, tableContent=
部位远处转移灶(个)

SUVmax值

FDG<FAPI(个)

SUVmax值

FDG≥FAPI(个)

合计16133
肺转移422
骨转移440
腹膜转移440
其他转移431
), ArticleFig(id=1194646641669018535, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493667946689, language=CN, label=表3, caption=

16个远处转移灶的18F-FDG和18F-FAPI PET/CT表现

, figureFileSmall=null, figureFileBig=null, tableContent=
部位远处转移灶(个)

SUVmax值

FDG<FAPI(个)

SUVmax值

FDG≥FAPI(个)

合计16133
肺转移422
骨转移440
腹膜转移440
其他转移431
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18F标记成纤维细胞活化蛋白抑制剂 PET/CT对18F-FDG摄取偏低恶性肿瘤的临床诊断价值
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梁志盈 , 林培颖 , 张汝森 , 李雯 , 李伟 *
解放军医学杂志 | 临床研究 2025,50(2): 154-161
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解放军医学杂志 | 临床研究 2025, 50(2): 154-161
18F标记成纤维细胞活化蛋白抑制剂 PET/CT对18F-FDG摄取偏低恶性肿瘤的临床诊断价值
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梁志盈, 林培颖, 张汝森, 李雯, 李伟*
作者信息
  • 广州医科大学附属肿瘤医院核医学科，广东广州 510095

    • 梁志盈，硕士研究生，主要从事肺肿瘤分子影像诊断方面的研究

通讯作者:

李伟，E-mail：
Clinical diagnosis value of 18F-fibroblast-activation protein inhibitor PET/CT in malignant tumors with low 18F-fluorodeoxyglucose uptake
Zhi-Ying Liang, Pei-Ying Lin, Ru-Sen Zhang, Wen Li, Wei Li*
Affiliations
  • Department of Nuclear Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, China
出版时间: 2025-02-28 doi: 10.11855/j.issn.0577-7402.1631.2024.0708
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摘要
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目的 探讨18F标记的成纤维细胞活化蛋白抑制剂(18F-FAPI)PET/CT对18F-氟代脱氧葡萄糖(18F-FDG)摄取偏低的恶性肿瘤的临床诊断价值。方法 前瞻性选取2021年1月－2022年11月在广州医科大学附属肿瘤医院确诊并接受18F-FAPI PET/CT检查的62例18F-FDG摄取偏低的恶性肿瘤患者。收集所有患者的一般信息、临床和影像资料。参照肿瘤邻近组织对18F-FDG和18F-FAPI的摄取水平，将肿瘤病灶分为高摄取、中摄取与低摄取，其中高摄取病灶设为阳性。记录并比较18F-FDG与18F-FAPI显示的肿瘤原发灶、转移灶数量及其摄取水平。结果 62例原发恶性肿瘤对18F-FDG低摄取18例(29.0%)、中摄取44例(71.0%)，而对18F-FAPI低摄取1例(1.6%)、中摄取6例(9.7%)、高摄取55例(88.7%)。原发肿瘤18F-FAPI的最大标准摄取值(SUVmax)明显高于18F-FDG(7.5±5.6 vs. 3.9±2.1，P<0.001)。18F-FAPI PET检出的阳性淋巴结数明显多于18F-FDG PET(77个 vs. 38个，P<0.01)。共检出16个远处转移灶，其中18F-FDG PET/CT检出11个(68.8%)，18F-FAPI PET/CT检出15个(93.8%)，两种示踪剂的检出率比较差异无统计学意义(P>0.05)。结论 对于18F-FDG摄取偏低的恶性肿瘤，18F-FAPI PET/CT可较好地显示肿瘤原发灶和转移灶。18F-FAPI可作为一种较有前景的放射性示踪剂，尤其适用于18F-FDG摄取偏低的恶性肿瘤。

18F标记的成纤维细胞活化蛋白抑制剂  /  18F-氟代脱氧葡萄糖  /  PET/CT  /  肿瘤  /  低摄取

Objective To evaluate the clinical value of 18F-fibroblast-activation protein inhibitor (18F-FAPI) PET/CT in malignant tumors exhibiting low uptake of 18F-fluorodeoxyglucose (18F-FDG). Methods We prospectively analyzed 62 patients with malignant tumors and low 18F-FDG uptake who underwent 18F-FAPI PET/CT in the Affiliated Cancer Hospital and Institute of Guangzhou Medical University from January 2021 to November 2022. Patient demographics information, clinical and radiological data were collected. Tumor lesions were categorized based on 18F-FAPI and 18F-FDG uptake relative to surrounding tissues into low-, moderate-, and high-uptake, with high uptake indicating positivity. The number and tracer uptake levels of primary tumors and metastatic lesions visualized by both 18F-FDG and 18F-FAPI were recorded and compared. Results Of the 62 primary tumors, 18(29.0%) showed low-uptake and 44 (71.0%) moderate-uptake on 18F-FDG PET, while 1(1.6%), 6(9.7%), and 55(88.7%) showed low, moderate, and high uptake on 18F-FAPI, respectively. The maximum standardized uptake value (SUVmax) for primary tumors was significantly higher with 18F-FAPI than with 18F-FDG (7.5±5.6 vs. 3.9±2.1, P<0.01). The number of positive lymph node foci revealed by 18F-FAPI was noticeably higher than that by 18F-FDG (77 vs. 38, P<0.01). A total of 16 distant organ metastases were identified, with 11(68.8%) detected by 18F-FDG and 15(93.8%) by 18F-FAPI, showing no significant difference in detection rates (P>0.05). Conclusions 18F-FAPI PET/CT effectively visualizes primary and metastatic lesions in malignant tumors with low 18F-FDG uptake, suggesting its potential as a promising radiotracer for such malignancies.

18F-fibroblast-activation protein inhibitors  /  18F-fluorodeoxyglucose  /  PET/CT  /  neoplasm  /  non-avidity
梁志盈, 林培颖, 张汝森, 李雯, 李伟. 18F标记成纤维细胞活化蛋白抑制剂 PET/CT对18F-FDG摄取偏低恶性肿瘤的临床诊断价值. 解放军医学杂志, 2025 , 50 (2) : 154 -161 . DOI: 10.11855/j.issn.0577-7402.1631.2024.0708
Zhi-Ying Liang, Pei-Ying Lin, Ru-Sen Zhang, Wen Li, Wei Li. Clinical diagnosis value of 18F-fibroblast-activation protein inhibitor PET/CT in malignant tumors with low 18F-fluorodeoxyglucose uptake[J]. Medical Journal of Chinese People’s Liberation Army, 2025 , 50 (2) : 154 -161 . DOI: 10.11855/j.issn.0577-7402.1631.2024.0708
正文
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肿瘤相关成纤维细胞(cancer-associated fibroblasts，CAFs)和细胞外纤维是肿瘤生长不可或缺的因素[1]。成纤维细胞活化蛋白(fibroblast-activation protein，FAP)在多种上皮癌的CAFs中过表达，而在正常组织中很少表达[2]。因此，可与肿瘤细胞特异性结合的FAP抑制剂(FAP inhibitors，FAPI)是一种新型肿瘤靶向放射性示踪剂，其已成为肿瘤核医学研究的热点。研究显示，FAPI可在肝癌、肺癌、胃癌等多种肿瘤中聚集并清晰地显示原发灶和转移灶[3-7]。18F-氟代脱氧葡萄糖(18F-fluorodeoxyglucose，18F-FDG)已广泛应用于恶性肿瘤的诊断和分期，但当肿瘤灶表现为18F-FDG低摄取时，其评估的敏感度和准确性会降低[8-11]。多项研究显示，FAPI因灵敏度高和本底摄取低，可检测到更多的肿瘤病灶，并更清晰地显示病灶[3-7]，有望成为比FDG更好的肿瘤示踪剂。目前肿瘤靶向放射性示踪剂的相关研究多使用68Ga标记FAPI，而较少使用18F。18F-FAPI PET/CT在肿瘤评估中的作用尚不清楚。本研究针对18F-FDG PET/CT低摄取的恶性肿瘤患者，探讨18F-FAPI PET/CT对肿瘤病变及其转移灶的临床检测价值。
1 资料与方法
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1.1 研究对象
前瞻性选取2021年1月－2022年11月在广州医科大学附属肿瘤医院确诊并接受18F-FAPI PET/CT检查的62例18F-FDG摄取偏低的恶性肿瘤患者。纳入标准：(1)常规影像学检查(CT、MRI或超声)检测到新发肿瘤；(2)18F-FDG PET/CT检查提示肿瘤灶对18F-FDG的摄取偏低(摄取水平低于或接近于周围本底组织)；(3)18F-FDG PET/CT检查后1周内接受了18F-FAPI PET/CT全身检查；(4)经病理检查或3个月以上的随访确诊为恶性肿瘤。排除标准：(1)妊娠期；(2)年龄<18岁；(3)18F-FAPI PET/CT检查前接受过化疗、放疗或靶向免疫治疗；(4)研究参与者、家属或法定代理人无法提供知情同意书。本研究获广州医科大学附属肿瘤医院医学伦理委员会审批(2021-sw07)，所有方法均遵守《赫尔辛基宣言》或等效的伦理标准。
1.2 18F-FDG和18F-FAPI的制备
18F-FDG和18F-FAPI由广州原子高科技有限公司合成。初产物用生理盐水进行洗脱，并通过0.22 μm微孔过滤器过滤至无菌多剂量注射器中灭菌，最终获得无菌、无热原的18F-FDG和18F-FAPI。两者的放射化学纯度均>95%。
1.3 PET/CT扫描
患者在18F-FDG PET/CT后1周内接受18F-FAPI PET/CT检查。所有PET/CT检查均在GE Discovery 710 PET/CT扫描仪上进行。18F-FDG PET/CT检查前，患者禁食≥6 h，血糖控制在<7.0 mmol/L(糖尿病患者控制在<11.1 mmol/L)。18F-FAPI PET/CT检查前无特殊准备。18F-FDG和18F-FAPI静脉注射剂量根据患者体重计算(3.7 MBq/kg)。注射后，使用PET/CT扫描仪采集图像，扫描范围为大腿上部至颅骨区域。首先获取CT图像，扫描参数为管电压120 kV，管电流100 mA，层厚3.75 mm，矩阵128×128，窗位7或8个；然后行PET采集，采用6~8个窗位、2.0~2.5 min/窗位、192×192矩阵的三维采集模式。最后将所有采集的数据传输到AW工作站进行图像融合及三维重建。
1.4 图像分析
在杏翔核医学报告系统软件(v1.0)上，由两名具有10年以上经验的核医学医师对所有PET、CT及PET/CT融合图像进行随机评估。若存在分歧，则通过协商达成一致。核医学医师需要鉴别原发肿瘤的位置，并评估其PET/CT特征。肿瘤灶的放射性水平采用最大标准摄取值(maximum standard uptake value，SUVmax)进行半定量分析，该值由计算机通过在PET/CT融合轴位图像上沿着肿瘤病灶边缘勾画感兴趣区域自动计算。参照肿瘤邻近组织对18F-FDG和18F-FAPI的摄取水平，通过视觉判断将肿瘤病灶分为高摄取、中摄取和低摄取，其中高摄取病灶设为阳性。原发肿瘤的CT表现分为三型：Ⅰ型，明显肿块或结节；Ⅱ型，软组织增厚或结构紊乱；Ⅲ型，无明显异常。
此外，记录每例患者18F-FDG和18F-FAPI显示的阳性淋巴结数量。所有远处转移灶按照受累器官进行分类，并记录其18F-FDG和18F-FAPI的SUVmax和阳性显示情况。
1.5 病灶诊断
原发肿瘤主要以组织病理学(穿刺或术后标本)为诊断标准。因伦理、医学或患者原因无法进行组织病理学检查时，则根据随访数据判断病变是否为恶性；例如，在化疗、放疗、靶向治疗或免疫治疗后3~13个月，CT/MRI图像显示病灶增大或数量增加，则认为疾病进展，病变判断为恶性。所有原发灶最终通过病理和(或)随访确诊为恶性肿瘤，所有转移病灶通过随访确诊。
1.6 统计学处理
采用SPSS 22.0软件进行统计分析。计量资料均符合正态分布，以x±s表示，组间比较采用配对样本t检验。计数资料以例(%)表示，组间比较采用χ2检验。P<0.05为差异有统计学意义。
2 结果
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2.1 一般资料
共纳入62例患者，男38例，女24例；年龄16~82岁，中位年龄55岁。62例患者最终经病理(39例)或随访(23例)诊断为恶性肿瘤。其中肝癌27例(43.5%)，胃癌10例(16.1%)，乳腺癌6例(9.7%)，口咽癌3例(4.8%)，肺癌、鼻咽癌、胰腺癌、胆囊癌、脑胶质瘤、淋巴瘤各2例(3.2%)，卵巢癌、阑尾癌、胸腺癌、十二指肠肉瘤各1例(1.6%)。62例原发肿瘤根据18F-FDG PET分为低摄取18例(29.0%)和中摄取44例(71.0%)；根据CT表现分为Ⅰ型37例(59.7%)、Ⅱ型16例(25.8%)、Ⅲ型9例(14.5%)。
2.2 原发肿瘤的检测结果
根据18F-FAPI摄取水平，62个原发肿瘤被分为低摄取1例(1.6%)、中摄取6例(9.7%)和高摄取55例(88.7%)。18F-FDG低摄取和中摄取的病灶分别有83.3%(15/18)和90.9%(40/44)在18F-FAPI上显示为阳性(高摄取)。肝癌、胃癌和乳腺癌中18F-FAPI高摄取者分别占85.2%(23/27)、90.0%(9/10)和100.0%(6/6)(图1－3)。原发灶18F-FDG的SUVmax明显低于18F-FAPI(3.9±2.1 vs. 7.5±5.6，P<0.001)。
由于样本量小，将部分肿瘤类型合并：3例口咽癌和2例鼻咽癌合并为咽部肿瘤，2例胰腺癌、2例胆囊癌、1例卵巢癌和1例阑尾癌合并为腹部肿瘤，2例肺癌和1例胸腺癌合并为胸部肿瘤，2例脑胶质瘤、2例淋巴瘤和1例十二指肠肉瘤合并为肉瘤。肝癌、胃癌、乳腺癌、口咽癌、腹部肿瘤和胸部肿瘤均表现为18F-FAPI的SUVmax高于18F-FDG(P<0.05，表1)。
此外，虽然肉瘤对18F-FAPI的SUVmax低于18F-FDG，但80%的肉瘤仍因为背景组织的摄取更低而显示为18F-FAPI阳性(高摄取，图4)。
2.3 阳性淋巴结检测结果
共18例患者在PET上检测到阳性淋巴结，其中胃癌6例(33.3%)，肝癌4例(22.2%)，乳腺癌4例(22.2%)。在这些患者中，18F-FDG共检测到38个阳性淋巴结，SUVmax为2.6~14.1(5.9±4.6)；而18F-FAPI检测到77个阳性淋巴结灶，SUVmax为3.2~14.3(8.3±3.7)。18F-FAPI PET检测到的阳性淋巴结灶明显多于18F-FDG PET(P<0.01，表2、图2)。
2.4 远处转移灶检测结果
12例恶性肿瘤患者确诊存在远处转移灶，其中肺转移4例，骨转移4例，腹膜转移4例，其他转移4例(肝转移、脑转移、胰腺转移、卵巢转移各1例)；共累及16个器官。16个转移灶中，18F-FDG PET/CT显示阳性11个(68.8%)，而18F-FAPI PET/CT显示阳性15个(93.8%)；两种示踪剂的检出率比较差异无统计学意义(P>0.05)。其中4个转移灶(2例骨转移、1例肝转移和1例胰腺转移)仅在18F-FAPI PET/CT中显示阳性，1例肝转移灶在18F-FDG和18F-FAPI PET/CT中均为低摄取。
16个远处转移灶18F-FDG和18F-FAPI的SUVmax分别为5.8±3.8和8.5±5.8，差异无统计学意义(P=0.083)；其中，SUVmaxFDG<FAPI 13个(81.3%)，FDG≥FAPI 3个(18.8%)(表3、图5)。
3 讨论
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多项研究显示，恶性肿瘤的18F-FDG低摄取可见于肝癌、肺癌、胃癌等常见肿瘤[9-11]。这些低摄取的病灶使18F-FDG在恶性肿瘤临床评估中的价值受到了一定限制。Seo等[9]报道18F-FDG PET/CT诊断肝内胆管癌淋巴结转移灶的特异度高达100%，但敏感度仅43%。Chandarana等[10]采用PET/CT评估肺结节，结果显示，34%(24/69)的结节不摄取18F-FDG。Ha等[11]发现，18F-FDG PET/CT诊断胃印戒细胞癌的敏感度仅为35.3%。本研究中，18F-FDG摄取偏低可见于多种类型的原发肿瘤，其中以肝癌(43.5%，27/62)和胃癌(16.1%，10/62)较为常见。因此，18F-FDG低摄取造成的肿瘤评估局限性值得临床关注，尤其是在肝癌和胃癌的评估中。
既往多项研究分析了肿瘤低摄取18F-FDG的原因，主要包括以下几个方面：(1)当肿瘤分化较好时，侵袭性较低，其糖代谢较低[12]；(2)己糖激酶-2在一些肿瘤细胞如胆管癌、胰腺癌、印戒细胞癌等低表达[13]；(3)一些本底摄取较高的组织如肝和大脑[14-15]等干扰了肿瘤的检测。FAPI的分布主要与肿瘤细胞中FAP的表达有关，几乎不受体内能量代谢和肌肉活动的影响，且大多数组织(包括肝和大脑)的FAPI本底通常较低[16]，因此，对于18F-FDG摄取低的肿瘤，FAPI在理论上具有良好的应用前景。本研究中大部分18F-FDG摄取偏低的肿瘤对18F-FAPI的SUVmax明显升高，仅肉瘤的SUVmax降低，但由于肉瘤周围本底摄取更低，因此其在18F-FAPI图像上仍清晰可见。
多项研究进行了FAPI与FDG的头对头对比，其中大部分比较68Ga-FAPI与18F-FDG在各种肿瘤诊断中的临床价值[17-20]。Guo等[19]报道，68Ga-FAPI对肝癌的检出率高于18F-FDG(87.4% vs. 65.0%)。Wang等[16]发现，68Ga-FAPI PET/CT对肺癌分期的诊断价值优于18F-FDG PET/CT。Chen等[20]对12例原发肿瘤的淋巴结转移灶进行检测发现，68Ga-FAPI的敏感度高于18F-FDG(86.4% vs. 45.5%)。Zhou等[18]对74例肺癌患者淋巴结转移灶的检测结果显示，68Ga-FAPI和18F-FDG的准确率分别为94%和30%。这些研究均提示68Ga-FAPI PET/CT有较高的临床价值。但鲜少有研究探讨18F-FAPI对18F-FDG低摄取肿瘤的临床应用价值。
迄今为止，相较于68Ga-FAPI，18F-FAPI的临床价值尚未得到广泛研究，仅有少量报道采用18F-FAPI评价各种肿瘤，包括肺癌[21]、胃癌[22]、甲状腺癌[23]、食管癌[24]等，且少有研究比较68Ga-FAPI与18F-FAPI的肿瘤诊断价值。Hu等[25]报道，在144个肿瘤病变中68Ga-FAPI和18F-FAPI的检出率相同，但18F-FAPI在肝脏、骨骼、淋巴结、胸膜和腹膜病变中显示出更高的靶本比。18F-FAPI对18F-FDG低摄取肿瘤的临床应用价值尚未得到系统性研究。本研究中，62例18F-FDG摄取偏低的恶性肿瘤中55例(88.7%)表现为18F-FAPI高摄取；18F-FAPI的淋巴结转移灶检出率是18F-FDG的2倍，对远处转移灶的检出率也高于18F-FDG(93.8% vs. 68.8%)，而且81.3%的远处转移灶在18F-FAPI PET/CT中表现出更高的SUVmax。近期的一项研究也认为，18F-FAPI PET/CT对于18F-FDG低摄取的良恶性病变鉴别具有较高的敏感度[26]。本研究结果提示，18F-FDG摄取偏低的肿瘤患者可受益于18F-FAPI PET/CT，主要体现在原发灶的显示和转移灶的检测方面。
本研究存在一定的局限性。首先，样本量相对较小，未来研究仍需进一步扩大；其次部分病例随访时间不长，其诊断结果与实际情况可能存在偏差；此外，本研究未进行18F-FAPI与68Ga-FAPI的对比，结果不能充分反映18F-FAPI的临床意义。这些局限性应在以后的研究中加以弥补。
综上所述，对于18F-FDG摄取偏低的恶性肿瘤，18F-FAPI PET/CT能更好地显示原发灶。18F-FAPI可作为一种具有良好应用前景的放射性示踪剂，尤其适用于18F-FDG摄取偏低的恶性肿瘤。
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doi: 10.11855/j.issn.0577-7402.1631.2024.0708
  • 接收时间：2023-12-09
  • 首发时间：2025-11-10
  • 出版时间：2025-02-28
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  • 收稿日期：2023-12-09
  • 录用日期：2024-05-11
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    广州医科大学附属肿瘤医院核医学科，广东广州 510095

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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