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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 13/2021

25.06.2021 | Original Article

State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis

verfasst von: Martina Sollini, Margarita Kirienko, Fabrizia Gelardi, Francesco Fiz, Noemi Gozzi, Arturo Chiti

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 13/2021

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Abstract

Introduction

Fibroblast activation protein-α (FAPα) is overexpressed on cancer-associated fibroblasts in approximately 90% of epithelial neoplasms, representing an appealing target for therapeutic and molecular imaging applications. [68 Ga]Ga-labelled radiopharmaceuticals—FAP-inhibitors (FAPI)—have been developed for PET. We systematically reviewed and meta-analysed published literature to provide an overview of its clinical role.

Materials and methods

The search, limited to January 1st, 2018–March 31st, 2021, was performed on MedLine and Embase databases using all the possible combinations of terms “FAP”, “FAPI”, “PET/CT”, “positron emission tomography”, “fibroblast”, “cancer-associated fibroblasts”, “CAF”, “molecular imaging”, and “fibroblast imaging”. Study quality was assessed using the QUADAS-2 criteria. Patient-based and lesion-based pooled sensitivities/specificities of FAPI PET were computed using a random-effects model directly from the STATA “metaprop” command. Between-study statistical heterogeneity was tested (I2-statistics).

Results

Twenty-three studies were selected for systematic review. Investigations on staging or restaging head and neck cancer (n = 2, 29 patients), abdominal malignancies (n = 6, 171 patients), various cancers (n = 2, 143 patients), and radiation treatment planning (n = 4, 56 patients) were included in the meta-analysis. On patient-based analysis, pooled sensitivity was 0.99 (95% CI 0.97–1.00) with negligible heterogeneity; pooled specificity was 0.87 (95% CI 0.62–1.00), with negligible heterogeneity. On lesion-based analysis, sensitivity and specificity had high heterogeneity (I2 = 88.56% and I2 = 97.20%, respectively). Pooled sensitivity for the primary tumour was 1.00 (95% CI 0.98–1.00) with negligible heterogeneity. Pooled sensitivity/specificity of nodal metastases had high heterogeneity (I2 = 89.18% and I2 = 95.74%, respectively). Pooled sensitivity in distant metastases was good (0.93 with 95% CI 0.88–0.97) with negligible heterogeneity.

Conclusions

FAPI-PET appears promising, especially in imaging cancers unsuitable for [18F]FDG imaging, particularly primary lesions and distant metastases. However, high-level evidence is needed to define its role, specifically to identify cancer types, non-oncological diseases, and clinical settings for its applications.
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Literatur
1.
Zurück zum Zitat Balkwill FR, Capasso M, Hagemann T. The tumor microenvironment at a glance. J Cell Sci. 2012;125:5591–6.PubMedCrossRef Balkwill FR, Capasso M, Hagemann T. The tumor microenvironment at a glance. J Cell Sci. 2012;125:5591–6.PubMedCrossRef
2.
Zurück zum Zitat Zhang Y, Weinberg RA. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities EMT: a naturally occurring transdifferentia-tion program. Front Med. 2018;12:1–13.CrossRef Zhang Y, Weinberg RA. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities EMT: a naturally occurring transdifferentia-tion program. Front Med. 2018;12:1–13.CrossRef
3.
Zurück zum Zitat Busek P, Mateu R, Zubal M, Kotackova L, Sedo A. Targeting fibroblast activation protein in cancer - Prospects and caveats. Front Biosci (Landmark Ed). 2018;23:1933–68.CrossRef Busek P, Mateu R, Zubal M, Kotackova L, Sedo A. Targeting fibroblast activation protein in cancer - Prospects and caveats. Front Biosci (Landmark Ed). 2018;23:1933–68.CrossRef
4.
Zurück zum Zitat Baghban R, Roshangar L, Jahanban-Esfahlan R, Seidi K, Ebrahimi-Kalan A, Jaymand M, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal. 2020;18(1):59. Baghban R, Roshangar L, Jahanban-Esfahlan R, Seidi K, Ebrahimi-Kalan A, Jaymand M, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal. 2020;18(1):59.
5.
Zurück zum Zitat LeBleu VS, Kalluri R. A peek into cancer-associated fibroblasts: origins, functions and translational impact. DMM Dis Model Mech. 2018;11:1–9. LeBleu VS, Kalluri R. A peek into cancer-associated fibroblasts: origins, functions and translational impact. DMM Dis Model Mech. 2018;11:1–9.
6.
Zurück zum Zitat Nurmik M, Ullmann P, Rodriguez F, Haan S, Letellier E. In search of definitions: cancer-associated fibroblasts and their markers. Int J Cancer. 2020;146:895–905.PubMedCrossRef Nurmik M, Ullmann P, Rodriguez F, Haan S, Letellier E. In search of definitions: cancer-associated fibroblasts and their markers. Int J Cancer. 2020;146:895–905.PubMedCrossRef
8.
Zurück zum Zitat Calais J. FAP: The next billion dollar nuclear theranostics target? J Nucl Med. 2020;61:163–5.PubMedCrossRef Calais J. FAP: The next billion dollar nuclear theranostics target? J Nucl Med. 2020;61:163–5.PubMedCrossRef
9.
Zurück zum Zitat Tillmanns J, Hoffmann D, Habbaba Y, Schmitto JD, Sedding D, Fraccarollo D, et al. Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction. J Mol Cell Cardiol. 2015;87:194–203.PubMedCrossRef Tillmanns J, Hoffmann D, Habbaba Y, Schmitto JD, Sedding D, Fraccarollo D, et al. Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction. J Mol Cell Cardiol. 2015;87:194–203.PubMedCrossRef
10.
Zurück zum Zitat Levy MT, McCaughan GW, Marinos G, Gorrell MD. Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infection. Liver. 2002;22:93–101.PubMedCrossRef Levy MT, McCaughan GW, Marinos G, Gorrell MD. Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infection. Liver. 2002;22:93–101.PubMedCrossRef
11.
Zurück zum Zitat Rettig WJ, Garin-Chesa P, Healey JH, Su SL, Jaffe EA, Old LJ. Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. Proc Natl Acad Sci U S A. 1992;89:10832–6.PubMedPubMedCentralCrossRef Rettig WJ, Garin-Chesa P, Healey JH, Su SL, Jaffe EA, Old LJ. Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. Proc Natl Acad Sci U S A. 1992;89:10832–6.PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Koczorowska MM, Tholen S, Bucher F, Lutz L, Kizhakkedathu JN, De Wever O, et al. Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations. Mol Oncol. 2016;10:40–58.PubMedCrossRef Koczorowska MM, Tholen S, Bucher F, Lutz L, Kizhakkedathu JN, De Wever O, et al. Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations. Mol Oncol. 2016;10:40–58.PubMedCrossRef
13.
Zurück zum Zitat Sedo A. Targeting fibroblast activation protein in cancer ndash Prospects and caveats. Front Biosci. 2018;23:4682.CrossRef Sedo A. Targeting fibroblast activation protein in cancer ndash Prospects and caveats. Front Biosci. 2018;23:4682.CrossRef
14.
Zurück zum Zitat Liu F, Qi L, Liu B, Liu J, Zhang H, Che D, et al. Fibroblast activation protein overexpression and clinical implications in solid tumors: a meta-analysis. Green J, editor. PLoS One. Public Library of Science; 2015;10:e0116683. Liu F, Qi L, Liu B, Liu J, Zhang H, Che D, et al. Fibroblast activation protein overexpression and clinical implications in solid tumors: a meta-analysis. Green J, editor. PLoS One. Public Library of Science; 2015;10:e0116683.
15.
Zurück zum Zitat Ebert LM, Yu W, Gargett T, Toubia J, Kollis PM, Tea MN, et al. Endothelial, pericyte and tumor cell expression in glioblastoma identifies fibroblast activation protein (FAP) as an excellent target for immunotherapy. Clin Transl Immunol. John Wiley & Sons, Ltd; 2020;9:e1191. Ebert LM, Yu W, Gargett T, Toubia J, Kollis PM, Tea MN, et al. Endothelial, pericyte and tumor cell expression in glioblastoma identifies fibroblast activation protein (FAP) as an excellent target for immunotherapy. Clin Transl Immunol. John Wiley & Sons, Ltd; 2020;9:e1191.
16.
Zurück zum Zitat Altmann A, Haberkorn U, Siveke J. The latest developments in imaging of fibroblast activation protein. J Nucl Med. 2021;62:160–7.PubMedCrossRef Altmann A, Haberkorn U, Siveke J. The latest developments in imaging of fibroblast activation protein. J Nucl Med. 2021;62:160–7.PubMedCrossRef
17.
Zurück zum Zitat Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. 68Ga-FAPI PET/CT: Tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801–5.PubMedPubMedCentralCrossRef Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. 68Ga-FAPI PET/CT: Tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801–5.PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Loktev A, Lindner T, Mier W, Debus J, Altmann A, Jäger D, et al. A tumor-imaging method targeting cancer-associated fibroblasts. J Nucl Med. Society of Nuclear Medicine and Molecular Imaging; 2018;59:1423–9. Loktev A, Lindner T, Mier W, Debus J, Altmann A, Jäger D, et al. A tumor-imaging method targeting cancer-associated fibroblasts. J Nucl Med. Society of Nuclear Medicine and Molecular Imaging; 2018;59:1423–9.
19.
Zurück zum Zitat Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.PubMedCrossRef Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.PubMedCrossRef
20.
Zurück zum Zitat Deeks JJ, Altman DG. Sensitivity and specificity and their confidence intervals cannot exceed 100%. BMJ BMJ. 1999;318:193–4.PubMedCrossRef Deeks JJ, Altman DG. Sensitivity and specificity and their confidence intervals cannot exceed 100%. BMJ BMJ. 1999;318:193–4.PubMedCrossRef
21.
Zurück zum Zitat Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. Arch Public Health; 2014;72:39. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. Arch Public Health; 2014;72:39.
22.
Zurück zum Zitat von Hippel PT. The heterogeneity statistic I2 can be biased in small meta-analyses. BMC Med Res Methodol. 2015;15:35.CrossRef von Hippel PT. The heterogeneity statistic I2 can be biased in small meta-analyses. BMC Med Res Methodol. 2015;15:35.CrossRef
24.
Zurück zum Zitat Luo Y, Pan Q, Yang H, Peng L, Zhang W, Li F. Fibroblast activation protein–targeted PET/CT with 68 Ga-FAPI for imaging IgG4-related disease: comparison to 18 F-FDG PET/CT. J Nucl Med. 2021;62:266–71.PubMedCrossRef Luo Y, Pan Q, Yang H, Peng L, Zhang W, Li F. Fibroblast activation protein–targeted PET/CT with 68 Ga-FAPI for imaging IgG4-related disease: comparison to 18 F-FDG PET/CT. J Nucl Med. 2021;62:266–71.PubMedCrossRef
25.
26.
Zurück zum Zitat Schmidkonz C, Rauber S, Atzinger A, Agarwal R, Götz TI, Soare A, et al. Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging. Ann Rheum Dis. 2020;79:1485–91.PubMedCrossRef Schmidkonz C, Rauber S, Atzinger A, Agarwal R, Götz TI, Soare A, et al. Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging. Ann Rheum Dis. 2020;79:1485–91.PubMedCrossRef
27.
Zurück zum Zitat Röhrich M, Floca R, Loi L, Adeberg S, Windisch P, Giesel FL, et al. FAP-specific PET signaling shows a moderately positive correlation with relative CBV and no correlation with ADC in 13 IDH wildtype glioblastomas. Eur J Radiol. 2020;127:109021.PubMedCrossRef Röhrich M, Floca R, Loi L, Adeberg S, Windisch P, Giesel FL, et al. FAP-specific PET signaling shows a moderately positive correlation with relative CBV and no correlation with ADC in 13 IDH wildtype glioblastomas. Eur J Radiol. 2020;127:109021.PubMedCrossRef
28.
Zurück zum Zitat Windisch P, Röhrich M, Regnery S, Tonndorf-Martini E, Held T, Lang K, et al. Fibroblast Activation Protein (FAP) specific PET for advanced target volume delineation in glioblastoma. Radiother Oncol. 2020;150:159–63.PubMedCrossRef Windisch P, Röhrich M, Regnery S, Tonndorf-Martini E, Held T, Lang K, et al. Fibroblast Activation Protein (FAP) specific PET for advanced target volume delineation in glioblastoma. Radiother Oncol. 2020;150:159–63.PubMedCrossRef
29.
Zurück zum Zitat Heckmann MB, Reinhardt F, Finke D, Katus HA, Haberkorn U, Leuschner F, et al. Relationship between cardiac fibroblast activation protein activity by positron emission tomography and cardiovascular disease. Circ Cardiovasc Imaging. 2020;13. Heckmann MB, Reinhardt F, Finke D, Katus HA, Haberkorn U, Leuschner F, et al. Relationship between cardiac fibroblast activation protein activity by positron emission tomography and cardiovascular disease. Circ Cardiovasc Imaging. 2020;13.
30.
Zurück zum Zitat Röhrich M, Naumann P, Giesel FL, Choyke PL, Staudinger F, Wefers A, et al. Impact of 68Ga-FAPI PET/CT Imaging on the therapeutic management of primary and recurrent pancreatic ductal adenocarcinomas. J Nucl Med. 2021;62:779–86.PubMedCrossRef Röhrich M, Naumann P, Giesel FL, Choyke PL, Staudinger F, Wefers A, et al. Impact of 68Ga-FAPI PET/CT Imaging on the therapeutic management of primary and recurrent pancreatic ductal adenocarcinomas. J Nucl Med. 2021;62:779–86.PubMedCrossRef
31.
Zurück zum Zitat Syed M, Flechsig P, Liermann J, Windisch P, Staudinger F, Akbaba S, et al. Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers. Eur J Nucl Med Mol Imaging. 2020;47:2836–45.PubMedPubMedCentralCrossRef Syed M, Flechsig P, Liermann J, Windisch P, Staudinger F, Akbaba S, et al. Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers. Eur J Nucl Med Mol Imaging. 2020;47:2836–45.PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Serfling S, Zhi Y, Schirbel A, Lindner T, Meyer T, Gerhard-Hartmann E, et al. Improved cancer detection in Waldeyer’s tonsillar ring by 68Ga-FAPI PET/CT imaging. Eur J Nucl Med Mol Imaging. 2021;48:1178–87.PubMedCrossRef Serfling S, Zhi Y, Schirbel A, Lindner T, Meyer T, Gerhard-Hartmann E, et al. Improved cancer detection in Waldeyer’s tonsillar ring by 68Ga-FAPI PET/CT imaging. Eur J Nucl Med Mol Imaging. 2021;48:1178–87.PubMedCrossRef
34.
Zurück zum Zitat Bergmann C, Distler JHW, Treutlein C, Tascilar K, Müller A-T, Atzinger A, et al. 68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study. Lancet Rheumatol. 2021;3:e185–94.CrossRef Bergmann C, Distler JHW, Treutlein C, Tascilar K, Müller A-T, Atzinger A, et al. 68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study. Lancet Rheumatol. 2021;3:e185–94.CrossRef
36.
Zurück zum Zitat Liermann J, Syed M, Ben-Josef E, Schubert K, Schlampp I, Sprengel SD, et al. Impact of FAPI-PET/CT on target volume definition in radiation therapy of locally recurrent pancreatic cancer. Cancers (Basel). 2021;13:796.CrossRef Liermann J, Syed M, Ben-Josef E, Schubert K, Schlampp I, Sprengel SD, et al. Impact of FAPI-PET/CT on target volume definition in radiation therapy of locally recurrent pancreatic cancer. Cancers (Basel). 2021;13:796.CrossRef
37.
Zurück zum Zitat Chen H, Pang Y, Wu J, Zhao L, Hao B, Wu J, et al. Comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. Eur J Nucl Med Mol Imaging. 2020;47:1820–32.PubMedCrossRef Chen H, Pang Y, Wu J, Zhao L, Hao B, Wu J, et al. Comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. Eur J Nucl Med Mol Imaging. 2020;47:1820–32.PubMedCrossRef
38.
Zurück zum Zitat Zhao L, Pang Y, Luo Z, Fu K, Yang T, Zhao L, et al. Role of [68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of peritoneal carcinomatosis and comparison with [18F]-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2021;48:1944–55.PubMedCrossRef Zhao L, Pang Y, Luo Z, Fu K, Yang T, Zhao L, et al. Role of [68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of peritoneal carcinomatosis and comparison with [18F]-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2021;48:1944–55.PubMedCrossRef
40.
Zurück zum Zitat Geist BK, Xing H, Wang J, Shi X, Zhao H, Hacker M, et al. A methodological investigation of healthy tissue, hepatocellular carcinoma, and other lesions with dynamic 68Ga-FAPI-04 PET/CT imaging. EJNMMI Phys. 2021;8:8.PubMedPubMedCentralCrossRef Geist BK, Xing H, Wang J, Shi X, Zhao H, Hacker M, et al. A methodological investigation of healthy tissue, hepatocellular carcinoma, and other lesions with dynamic 68Ga-FAPI-04 PET/CT imaging. EJNMMI Phys. 2021;8:8.PubMedPubMedCentralCrossRef
41.
Zurück zum Zitat Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of 68Ga-FAPI and 18F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021;298:393–402.PubMedCrossRef Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of 68Ga-FAPI and 18F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021;298:393–402.PubMedCrossRef
42.
Zurück zum Zitat Chen H, Zhao L, Ruan D, Pang Y, Hao B, Dai Y, et al. Usefulness of [68Ga]Ga-DOTA-FAPI-04 PET/CT in patients presenting with inconclusive [18F]FDG PET/CT findings. Eur J Nucl Med Mol Imaging. 2021;48:73–86.PubMedCrossRef Chen H, Zhao L, Ruan D, Pang Y, Hao B, Dai Y, et al. Usefulness of [68Ga]Ga-DOTA-FAPI-04 PET/CT in patients presenting with inconclusive [18F]FDG PET/CT findings. Eur J Nucl Med Mol Imaging. 2021;48:73–86.PubMedCrossRef
43.
Zurück zum Zitat Zhao L, Chen S, Chen S, Pang Y, Dai Y, Hu S, et al. 68Ga-fibroblast activation protein inhibitor PET/CT on gross tumour volume delineation for radiotherapy planning of oesophageal cancer. Radiother Oncol. 2021;158:55–61.PubMedCrossRef Zhao L, Chen S, Chen S, Pang Y, Dai Y, Hu S, et al. 68Ga-fibroblast activation protein inhibitor PET/CT on gross tumour volume delineation for radiotherapy planning of oesophageal cancer. Radiother Oncol. 2021;158:55–61.PubMedCrossRef
44.
Zurück zum Zitat Shi X, Xing H, Yang X, Li F, Yao S, Congwei J, et al. Comparison of PET imaging of activated fibroblasts and 18F-FDG for diagnosis of primary hepatic tumours: a prospective pilot study. Eur J Nucl Med Mol Imaging. 2021;48:1593–603.PubMedCrossRef Shi X, Xing H, Yang X, Li F, Yao S, Congwei J, et al. Comparison of PET imaging of activated fibroblasts and 18F-FDG for diagnosis of primary hepatic tumours: a prospective pilot study. Eur J Nucl Med Mol Imaging. 2021;48:1593–603.PubMedCrossRef
45.
Zurück zum Zitat Shi X, Xing H, Yang X, Li F, Yao S, Zhang H, et al. Fibroblast imaging of hepatic carcinoma with 68Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules. Eur J Nucl Med Mol Imaging. Springer; 2020;1–8. Shi X, Xing H, Yang X, Li F, Yao S, Zhang H, et al. Fibroblast imaging of hepatic carcinoma with 68Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules. Eur J Nucl Med Mol Imaging. Springer; 2020;1–8.
46.
Zurück zum Zitat Guo W, Pang Y, Yao L, Zhao L, Fan C, Ke J, 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. Eur J Nucl Med Mol Imaging. 2021;48:1604–17.PubMedCrossRef Guo W, Pang Y, Yao L, Zhao L, Fan C, Ke J, 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. Eur J Nucl Med Mol Imaging. 2021;48:1604–17.PubMedCrossRef
47.
Zurück zum Zitat Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of 68 Ga-FAPI and 18 F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021;298:393–402.PubMedCrossRef Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of 68 Ga-FAPI and 18 F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021;298:393–402.PubMedCrossRef
48.
Zurück zum Zitat Moradi F, Iagaru A. Will FAPI PET/CT replace FDG PET/CT in the next decade? Counterpoint—no, not so fast! Am J Roentgenol. 2021;216:307–8.CrossRef Moradi F, Iagaru A. Will FAPI PET/CT replace FDG PET/CT in the next decade? Counterpoint—no, not so fast! Am J Roentgenol. 2021;216:307–8.CrossRef
49.
Zurück zum Zitat Calais J, Mona CE. Will FAPI PET/CT replace FDG PET/CT in the next decade? Point—an important diagnostic, phenotypic, and biomarker role. Am J Roentgenol. 2021;216:305–6.CrossRef Calais J, Mona CE. Will FAPI PET/CT replace FDG PET/CT in the next decade? Point—an important diagnostic, phenotypic, and biomarker role. Am J Roentgenol. 2021;216:305–6.CrossRef
50.
Zurück zum Zitat Guglielmo P, Guerra L. Radiolabeled fibroblast activation protein inhibitor (FAPI) PET in oncology: has the time come for 18F-fluorodeoxyglucose to think to a well-deserved retirement? Clin Transl Imaging. 2021;9:1–2.CrossRef Guglielmo P, Guerra L. Radiolabeled fibroblast activation protein inhibitor (FAPI) PET in oncology: has the time come for 18F-fluorodeoxyglucose to think to a well-deserved retirement? Clin Transl Imaging. 2021;9:1–2.CrossRef
51.
Zurück zum Zitat Hicks RJ, Roselt PJ, Kallur KG, Tothill RW, Mileshkin L. FAPI PET/CT: will it end the hegemony of 18 F-FDG in oncology? J Nucl Med. 2021;62:296–302.PubMedCrossRef Hicks RJ, Roselt PJ, Kallur KG, Tothill RW, Mileshkin L. FAPI PET/CT: will it end the hegemony of 18 F-FDG in oncology? J Nucl Med. 2021;62:296–302.PubMedCrossRef
53.
Zurück zum Zitat Kitajima K, Nakajo M, Kaida H, Minamimoto R, Hirata K, Tsurusaki M, et al. Present and future roles of FDG-PET/CT imaging in the management of gastrointestinal cancer: An update. Nagoya J Med Sci. 2017;79:527–43.PubMedPubMedCentral Kitajima K, Nakajo M, Kaida H, Minamimoto R, Hirata K, Tsurusaki M, et al. Present and future roles of FDG-PET/CT imaging in the management of gastrointestinal cancer: An update. Nagoya J Med Sci. 2017;79:527–43.PubMedPubMedCentral
54.
Zurück zum Zitat Zhao C, Zhang Y, Wang J. A meta-analysis on the diagnostic performance of (18)F-FDG and (11)C-methionine PET for differentiating brain tumors. AJNR Am J Neuroradiol. American Society of Neuroradiology; 2014;35:1058–65. Zhao C, Zhang Y, Wang J. A meta-analysis on the diagnostic performance of (18)F-FDG and (11)C-methionine PET for differentiating brain tumors. AJNR Am J Neuroradiol. American Society of Neuroradiology; 2014;35:1058–65.
55.
Zurück zum Zitat Borggreve AS, Goense L, Brenkman HJF, Mook S, Meijer GJ, Wessels FJ, et al. Imaging strategies in the management of gastric cancer: current role and future potential of MRI. Br J Radiol. 2019;92:20181044.PubMedPubMedCentralCrossRef Borggreve AS, Goense L, Brenkman HJF, Mook S, Meijer GJ, Wessels FJ, et al. Imaging strategies in the management of gastric cancer: current role and future potential of MRI. Br J Radiol. 2019;92:20181044.PubMedPubMedCentralCrossRef
56.
Zurück zum Zitat Gauthé M, Richard-Molard M, Cacheux W, Michel P, Jouve J-L, Mitry E, et al. Role of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography in gastrointestinal cancers. Dig Liver Dis Dig Liver Dis. 2015;47:443–54.PubMedCrossRef Gauthé M, Richard-Molard M, Cacheux W, Michel P, Jouve J-L, Mitry E, et al. Role of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography in gastrointestinal cancers. Dig Liver Dis Dig Liver Dis. 2015;47:443–54.PubMedCrossRef
57.
Zurück zum Zitat Zi F, He J, He D, Li Y, Yang L, Cai Z. Fibroblast activation protein α in tumor microenvironment: recent progression and implications (review). Mol Med Rep. 2015;11:3203–11.PubMedPubMedCentralCrossRef Zi F, He J, He D, Li Y, Yang L, Cai Z. Fibroblast activation protein α in tumor microenvironment: recent progression and implications (review). Mol Med Rep. 2015;11:3203–11.PubMedPubMedCentralCrossRef
58.
Zurück zum Zitat Mamoor S. FAP is differentially expressed in lymph node metastasis in human breast cancer. OSF Preprints. Mamoor S. FAP is differentially expressed in lymph node metastasis in human breast cancer. OSF Preprints.
59.
Zurück zum Zitat Cremasco V, Astarita JL, Grauel AL, Keerthivasan S, MacIsaac K, Woodruff MC, et al. FAP delineates heterogeneous and functionally divergent stromal cells in immune-excluded breast tumors. Cancer Immunol Res. 2018;6:1472–85.PubMedPubMedCentralCrossRef Cremasco V, Astarita JL, Grauel AL, Keerthivasan S, MacIsaac K, Woodruff MC, et al. FAP delineates heterogeneous and functionally divergent stromal cells in immune-excluded breast tumors. Cancer Immunol Res. 2018;6:1472–85.PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat Pelon F, Bourachot B, Kieffer Y, Magagna I, Mermet-Meillon F, Bonnet I, et al. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat Commun. 2020;11:404.PubMedPubMedCentralCrossRef Pelon F, Bourachot B, Kieffer Y, Magagna I, Mermet-Meillon F, Bonnet I, et al. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat Commun. 2020;11:404.PubMedPubMedCentralCrossRef
63.
Zurück zum Zitat Hao B, Wu J, Pang Y, Sun L, Chen H. 68Ga-FAPI PET/CT in assessment of leptomeningeal metastases in a patient with lung adenocarcinoma. Clin Nucl Med Clin Nucl Med. 2020;45:784–6.PubMedCrossRef Hao B, Wu J, Pang Y, Sun L, Chen H. 68Ga-FAPI PET/CT in assessment of leptomeningeal metastases in a patient with lung adenocarcinoma. Clin Nucl Med Clin Nucl Med. 2020;45:784–6.PubMedCrossRef
64.
Zurück zum Zitat Luo Y, Pan Q, Yang H, Li F, Zhang F. Inflammatory arthritis induced by anti-programmed death-1 shown in 68Ga-FAPI PET/CT in a patient with esophageal carcinoma. Clin Nucl Med Clin Nucl Med. 2021;46:431–2.PubMedCrossRef Luo Y, Pan Q, Yang H, Li F, Zhang F. Inflammatory arthritis induced by anti-programmed death-1 shown in 68Ga-FAPI PET/CT in a patient with esophageal carcinoma. Clin Nucl Med Clin Nucl Med. 2021;46:431–2.PubMedCrossRef
65.
Zurück zum Zitat Foster DS, Nguyen AT, Chinta M, Titan AL, Salhotra A, Jones RE, et al. Cancer-associated fibroblasts persist but show decreased fibroblast activation protein expression after neoadjuvant chemotherapy in human pancreatic ductal adenocarcinoma. J Am Coll Surg Elsevier. 2019;229:S257–8.CrossRef Foster DS, Nguyen AT, Chinta M, Titan AL, Salhotra A, Jones RE, et al. Cancer-associated fibroblasts persist but show decreased fibroblast activation protein expression after neoadjuvant chemotherapy in human pancreatic ductal adenocarcinoma. J Am Coll Surg Elsevier. 2019;229:S257–8.CrossRef
66.
Zurück zum Zitat Ansems M, Span PN. The tumor microenvironment and radiotherapy response; a central role for cancer-associated fibroblasts. Clin Transl Radiat Oncol Elsevier. 2020;22:90–7. Ansems M, Span PN. The tumor microenvironment and radiotherapy response; a central role for cancer-associated fibroblasts. Clin Transl Radiat Oncol Elsevier. 2020;22:90–7.
67.
Zurück zum Zitat Donlon NE, Power R, Hayes C, Reynolds JV, Lysaght J. Radiotherapy, immunotherapy, and the tumour microenvironment: turning an immunosuppressive milieu into a therapeutic opportunity. Cancer Lett Elsevier. 2021;502:84–96.CrossRef Donlon NE, Power R, Hayes C, Reynolds JV, Lysaght J. Radiotherapy, immunotherapy, and the tumour microenvironment: turning an immunosuppressive milieu into a therapeutic opportunity. Cancer Lett Elsevier. 2021;502:84–96.CrossRef
68.
Zurück zum Zitat Piper M, Mueller AC, Karam SD. The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy. Mol Carcinog. John Wiley & Sons, Ltd; 2020;59:754–65. Piper M, Mueller AC, Karam SD. The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy. Mol Carcinog. John Wiley & Sons, Ltd; 2020;59:754–65.
69.
Zurück zum Zitat Jin M-Z, Jin W-L. The updated landscape of tumor microenvironment and drug repurposing. Signal Transduct Target Ther. Nature Publishing Group; 2020;5:166. Jin M-Z, Jin W-L. The updated landscape of tumor microenvironment and drug repurposing. Signal Transduct Target Ther. Nature Publishing Group; 2020;5:166.
70.
Zurück zum Zitat Windisch P, Zwahlen DR, Giesel FL, Scholz E, Lugenbiel P, Debus J, et al. Clinical results of fibroblast activation protein (FAP) specific PET for non-malignant indications: systematic review. EJNMMI Res. 2021;11:18.PubMedPubMedCentralCrossRef Windisch P, Zwahlen DR, Giesel FL, Scholz E, Lugenbiel P, Debus J, et al. Clinical results of fibroblast activation protein (FAP) specific PET for non-malignant indications: systematic review. EJNMMI Res. 2021;11:18.PubMedPubMedCentralCrossRef
71.
Zurück zum Zitat Gu B, Luo Z, He X, Wang J, Song S. 68Ga-FAPI and 18F-FDG PET/CT images in a patient with extrapulmonary tuberculosis mimicking malignant tumor. Clin Nucl Med Clin Nucl Med. 2020;45:865–7.PubMedCrossRef Gu B, Luo Z, He X, Wang J, Song S. 68Ga-FAPI and 18F-FDG PET/CT images in a patient with extrapulmonary tuberculosis mimicking malignant tumor. Clin Nucl Med Clin Nucl Med. 2020;45:865–7.PubMedCrossRef
73.
Zurück zum Zitat Hao B, Wu X, Pang Y, Sun L, Wu H, Huang W, et al. [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of tuberculous lesions. Eur J Nucl Med Mol Imaging. Springer; 2021;48:651–2. Hao B, Wu X, Pang Y, Sun L, Wu H, Huang W, et al. [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of tuberculous lesions. Eur J Nucl Med Mol Imaging. Springer; 2021;48:651–2.
74.
Zurück zum Zitat Zhu W, Guo F, Wang Y, Ding H, Huo L. 68Ga-FAPI-04 accumulation in myocardial infarction in a patient with neuroendocrine carcinoma. Clin Nucl Med Clin Nucl Med. 2020;45:1020–2.PubMedCrossRef Zhu W, Guo F, Wang Y, Ding H, Huo L. 68Ga-FAPI-04 accumulation in myocardial infarction in a patient with neuroendocrine carcinoma. Clin Nucl Med Clin Nucl Med. 2020;45:1020–2.PubMedCrossRef
75.
Zurück zum Zitat Notohamiprodjo S, Nekolla SG, Robu S, Villagran Asiares A, Kupatt C, Ibrahim T, et al. Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04. J Nucl Cardiol. J Nucl Cardiol; 2021. Notohamiprodjo S, Nekolla SG, Robu S, Villagran Asiares A, Kupatt C, Ibrahim T, et al. Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04. J Nucl Cardiol. J Nucl Cardiol; 2021.
76.
Zurück zum Zitat Luo Y, Pan Q, Xu H, Zhang R, Li J, Li F. Active uptake of 68Ga-FAPI in Crohn’s disease but not in ulcerative colitis. Eur J Nucl Med Mol Imaging. 2021;48:1682–3.PubMedCrossRef Luo Y, Pan Q, Xu H, Zhang R, Li J, Li F. Active uptake of 68Ga-FAPI in Crohn’s disease but not in ulcerative colitis. Eur J Nucl Med Mol Imaging. 2021;48:1682–3.PubMedCrossRef
77.
Zurück zum Zitat Wu S, Pang Y, Chen Y, Sun H, Chen H. 68Ga-DOTA-FAPI-04 PET/CT in Erdheim-Chester Disease. Clin Nucl Med Clin Nucl Med. 2021;46:258–60.PubMedCrossRef Wu S, Pang Y, Chen Y, Sun H, Chen H. 68Ga-DOTA-FAPI-04 PET/CT in Erdheim-Chester Disease. Clin Nucl Med Clin Nucl Med. 2021;46:258–60.PubMedCrossRef
78.
Zurück zum Zitat Xu T, Zhao Y, Ding H, Cai L, Zhou Z, Song Z, et al. [68Ga]Ga-DOTA-FAPI-04 PET/CT imaging in a case of prostate cancer with shoulder arthritis. Eur J Nucl Med Mol Imaging. Springer; 2021;48:1254–5. Xu T, Zhao Y, Ding H, Cai L, Zhou Z, Song Z, et al. [68Ga]Ga-DOTA-FAPI-04 PET/CT imaging in a case of prostate cancer with shoulder arthritis. Eur J Nucl Med Mol Imaging. Springer; 2021;48:1254–5.
79.
Zurück zum Zitat Pan Q, Luo Y, Zhang W. Idiopathic retroperitoneal fibrosis with intense uptake of 68Ga-fibroblast activation protein inhibitor and 18F-FDG. Clin Nucl Med Clin Nucl Med. 2021;46:175–6.PubMedCrossRef Pan Q, Luo Y, Zhang W. Idiopathic retroperitoneal fibrosis with intense uptake of 68Ga-fibroblast activation protein inhibitor and 18F-FDG. Clin Nucl Med Clin Nucl Med. 2021;46:175–6.PubMedCrossRef
81.
Zurück zum Zitat Can C, Gündoğan C, Güzel Y, Kaplan İ, Kömek H. 68Ga-FAPI uptake of thyroiditis in a patient with breast cancer. Clin Nucl Med. Clin Nucl Med; 2021;Publish Ah. Can C, Gündoğan C, Güzel Y, Kaplan İ, Kömek H. 68Ga-FAPI uptake of thyroiditis in a patient with breast cancer. Clin Nucl Med. Clin Nucl Med; 2021;Publish Ah.
82.
Zurück zum Zitat Zhou Y, He J, Chen Y. 68Ga-FAPI PET/CT imaging in a patient with thyroiditis. Endocrine. Springer; 2021;1–2. Zhou Y, He J, Chen Y. 68Ga-FAPI PET/CT imaging in a patient with thyroiditis. Endocrine. Springer; 2021;1–2.
83.
Zurück zum Zitat Zhou Y, Yang X, Liu H, Luo W, Liu H, Lv T, et al. Value of [68Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis. Eur J Nucl Med Mol Imaging. Eur J Nucl Med Mol Imaging; 2021. Zhou Y, Yang X, Liu H, Luo W, Liu H, Lv T, et al. Value of [68Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis. Eur J Nucl Med Mol Imaging. Eur J Nucl Med Mol Imaging; 2021.
84.
Zurück zum Zitat Liu H, Chen Z, Yang X, Fu W, Chen Y. Increased 68Ga-FAPI uptake in chronic cholecystitis and degenerative osteophyte. Clin Nucl Med. Clin Nucl Med; 2021;Publish Ah. Liu H, Chen Z, Yang X, Fu W, Chen Y. Increased 68Ga-FAPI uptake in chronic cholecystitis and degenerative osteophyte. Clin Nucl Med. Clin Nucl Med; 2021;Publish Ah.
85.
Zurück zum Zitat Wu J, Liu H, Ou L, Jiang G, Zhang C. FAPI uptake in a vertebral body fracture in a patient with lung cancer: a FAPI imaging pitfall. Clin Nucl Med Clin Nucl Med. 2021;46:520–2.PubMedCrossRef Wu J, Liu H, Ou L, Jiang G, Zhang C. FAPI uptake in a vertebral body fracture in a patient with lung cancer: a FAPI imaging pitfall. Clin Nucl Med Clin Nucl Med. 2021;46:520–2.PubMedCrossRef
87.
Zurück zum Zitat Saunders NA, Simpson F, Thompson EW, Hill MM, Endo-Munoz L, Leggatt G, et al. Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives. EMBO Mol Med EMBO Mol Med. 2012;4:675–84.PubMedCrossRef Saunders NA, Simpson F, Thompson EW, Hill MM, Endo-Munoz L, Leggatt G, et al. Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives. EMBO Mol Med EMBO Mol Med. 2012;4:675–84.PubMedCrossRef
88.
Zurück zum Zitat Miao L, Lin CM, Huang L. Stromal barriers and strategies for the delivery of nanomedicine to desmoplastic tumors. J Control Release J Control Release. 2015;219:192–204.PubMedCrossRef Miao L, Lin CM, Huang L. Stromal barriers and strategies for the delivery of nanomedicine to desmoplastic tumors. J Control Release J Control Release. 2015;219:192–204.PubMedCrossRef
89.
Zurück zum Zitat Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18:99–115.PubMedCrossRef Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18:99–115.PubMedCrossRef
90.
Zurück zum Zitat Gelardi F, Kirienko M, Sollini M. Climbing the steps of the evidence-based medicine pyramid: highlights from Annals of Nuclear Medicine 2019. Eur J Nucl Med Mol Imaging. 2021;48:1293–301.PubMedCrossRef Gelardi F, Kirienko M, Sollini M. Climbing the steps of the evidence-based medicine pyramid: highlights from Annals of Nuclear Medicine 2019. Eur J Nucl Med Mol Imaging. 2021;48:1293–301.PubMedCrossRef
91.
Zurück zum Zitat Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of 177 Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. Massachusetts Medical Society; 2017;376:125–35. Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of 177 Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. Massachusetts Medical Society; 2017;376:125–35.
92.
Zurück zum Zitat Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet Elsevier. 2021;397:797–804.CrossRef Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet Elsevier. 2021;397:797–804.CrossRef
Metadaten
Titel
State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis
verfasst von
Martina Sollini
Margarita Kirienko
Fabrizia Gelardi
Francesco Fiz
Noemi Gozzi
Arturo Chiti
Publikationsdatum
25.06.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 13/2021
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05475-0

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