It’s all about FAPI – aktuelle Anwendungen der FAPI-PET

Zusammenfassung

Das Fibroblasten-Aktivierungsprotein α (FAPα) hat sich als vielversprechende Zielstruktur in der molekularen Bildgebung mittels PET/CT etabliert. Es wird überwiegend von tumorassoziierten Fibroblasten im Tumormikromilieu exprimiert und trägt über die Förderung von Tumorwachstum, Immunsuppression und Angiogenese zur Resistenzentwicklung gegenüber systemischen Therapien bei. Die Entwicklung FAPα-gerichteter Radioliganden ermöglicht die nicht-invasive Visualisierung dieser Zielstruktur. Aufgrund der Expression in über 90 % aller epithelialen Tumoren sowie bei fibrotischen und inflammatorischen Prozessen bietet die FAPI-PET/CT ein breites Anwendungsspektrum sowohl für maligne („Pan-Tumor“-Radioligand) als auch benigne Erkrankungen. Die derzeitige Evidenzlage basiert überwiegend auf retrospektiven Analysen. Für die Etablierung in der klinischen Routine sind prospektive Studien erforderlich, die die Korrelation zwischen Bildgebung und immunhistochemischer FAPα-Expression belegen und den diagnostischen Zusatznutzen der FAPI-PET/CT gegenüber konventionellen Verfahren bestätigen. Die kürzlich publizierte Leitlinie zur FAPα-Bildgebung unterstreicht die wachsende klinische Relevanz dieses Ansatzes und stellt einen wichtigen Meilenstein dar.

Abstract

Fibroblast activation protein α (FAPα) has emerged as a promising molecular target for PET/CT imaging. Predominantly expressed by cancer-associated fibroblasts within the tumor microenvironment, FAPα promotes tumor growth, immunosuppression, and angiogenesis, thereby contributing to resistance against systemic therapies. The development of FAPα-targeted radioligands enables non-invasive visualization of this protein. Given its expression in over 90% of epithelial tumors, as well as in fibrotic and inflammatory conditions, FAPI-PET/CT offers a broad diagnostic spectrum, for both malignant (“Pan-Tumor”-Radioligand) and benign diseases. However, current evidence is largely based on retrospective analyses. Prospective studies are required to establish FAPI-PET/CT in clinical practice by demonstrating correlations between imaging and immunohistochemical FAPα expression, as well as its diagnostic advantage over conventional imaging modalities. The recently published guideline on FAPα-targeted imaging highlights the growing clinical relevance of this approach and represents an important milestone.

Schlüsselwörter

FAPI-PET - molekulare Bildgebung - Onkologie

Keywords

FAPI-PET - molecular imaging - Oncology

Publikationsverlauf

Artikel online veröffentlicht:
02. September 2025

• Referenzen:

• 1 Hope TA, Calais J, Goenka AH. et al. SNMMI Procedure Standard/EANM Practice Guideline for Fibroblast Activation Protein (FAP) PET. J Nucl Med 2025; 66: 26-33
• 2 Zi F, He J, He D. et al. Fibroblast activation protein α in tumor microenvironment: Recent progression and implications (Review). Mol Med Rep 2015; 11: 3203-3211
• 3 Hamson EJ, Keane FM, Tholen S. et al. Understanding fibroblast activation protein (FAP) substrates, activities, expression and targeting for cancer therapy. Proteomics Clin Appl 2014; 8: 454-463
• 4 Dohi O, Ohtani H, Hatori M. et al. Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours. Histopathology 2009; 55: 432-440
• 5 Scanlan MJ, Raj BKM, Calvo B. et al. Molecular cloning of fibroblast activation protein α, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA 1994; 91: 5657-5661
• 6 Dendl K, Koerber SA, Kratochwil C. et al. FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?. Cancers (Basel) 2021; 13: 4946
• 7 Levy MT, Mccaughan G, Abbott C. Fibroblast activation protein: A cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis. Hepatology 1999; 29: 1768-1778
• 8 Bauer S, Jendro MC, Wadle A. et al. Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes. Arthritis Res 2006; 8: R171
• 9 Loktev A, Lindner T, Mier W. et al. A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts. J Nucl Med 2018; 59: 1423-1429
• 10 Zi F, He J, He D. et al. Fibroblast activation protein α in tumor microenvironment: recent progression and implications (review). Mol Med Rep 2015; 11: 3203-3211
• 11 Kelly T. Fibroblast activation protein-alpha and dipeptidyl peptidase IV (CD26): cell-surface proteases that activate cell signaling and are potential targets for cancer therapy. Drug Resist Updat 2005; 8: 51-58
• 12 Chen WT, Kelly T. Seprase complexes in cellular invasiveness. Cancer Metastasis Rev 2008; 22: 259-269
• 13 Kuzet S-E, Gaggiolo C. Fibroblast activation in cancer: when seed fertilizes soil. Cell Tissue Res 2016; 365: 607-619
• 14 Zhang Y, Tang H, Cai J. et al. Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett 2011; 303: 47-55
• 15 Henry LR, Lee HO, Klein-Szanto A. et al. Clinical Implications of Fibroblast Activation Protein in Patients with Colon Cancer. Clin Cancer Res 2007; 13: 1736-1741
• 16 Kratochwil C, Flechsig P, Lindner T. et al. 68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer. J Nucl Med 2019; 60: 801-805
• 17 Loktev A, Lindner T, Burger EM. et al. Development of Fibroblast Activation Protein-Targeted Radiotracers with Improved Tumor Retention. J Nucl Med 2019; 60: 1421-1429
• 18 Giesel FL, Adeberg S, Syed M. et al. FAPI-74 PET/CT Using Either 18F-AIF or Cold-Kit 68Ga Labelling: Biodistribution, Radiation Dosimetry, and Tumor Delineation in Lung Cancer Patients. J Nucl Med 2021; 62: 201-207
• 19 Millul J, Koepke L, Raghuvir Haridas G. et al. Head-to-head comparison of different classes of FAP radioligands designed to increase tumor residence time: monomer, dimer, albumin binders, and small molecules vs peptides. Eur J Nucl Med Mol Imaging 2023; 50: 3050-3061
• 20 Galbiati A, Bocci M, Ravazza D. et al. Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors. J Nucl Med 2024; 65: 1604-1610
• 21 Baum RP, 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 Nucl Med 2022; 63: 415-423
• 22 Bergquist A, von Seth E. Epidemiology of cholangiocarcinoma. Semin Liver Dis 2004; 24: 115-125
• 23 Pabst KM, Trajkovic-Arsic M, Cheung PFY. et al. Superior Tumor Detection for 68Ga-FAPI-46 Versus 18F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma. J Nucl Med 2023; 64: 1049-1055
• 24 Weiberg D, Felgenhauer T, Czerner CP. et al. 68Ga-FAPI-46-PET/CT in Primary Sclerosing Cholangitis with Suspected Cholangiocarcinoma. Eur J Nucl Med Mol Imaging 2024; 51: 1-1026
• 25 Kessler L, Hirmas N, Pabst KM. et al. 68Ga-Labeled Fibroblast Activation Protein Inhibitor (68Ga-FAPI) PET for Pancreatic Adenocarcinoma: Data from the 68Ga-FAPI PET Observational Trial. J Nucl Med 2023; 64: 1910-1917
• 26 Demmert TT, Pomykala KL, Lanzafame H. et al. Oncologic Staging with 68Ga-FAPI PET/CT Demonstrates a Lower Rate of Nonspecific Lymph Node Findings Than 18F-FDG PET/CT. J Nucl Med 2023; 64: 1906-1909
• 27 Lanzafame H, Mavroeidi IA, Pabst KM. et al. 68Ga-Fibroblast Activation Protein Inhibitor PET/CT Improves Detection of Intermediate and Low-Grade Sarcomas and Identifies Candidates for Radiopharmaceutical Therapy. J Nucl Med 2024; 65: 880-887
• 28 Hotta M, Kim GHJ, Rerkpichaisuth V. et al. Correlation of FAPI PET Uptake with Immunohistochemistry in Explanted Lungs from Patients with Advanced Interstitial Lung Diseases. J Nucl Med 2024; 65: 1789-1794
• 29 Popescu CE, Ferro P, Gotuzzo I. et al. 68Ga-FAPi: Pathways and Diagnosis in Cardiac Imaging. Curr Cardiovasc Imaging Rep 2023; 16: 93-101
• 30 Liu H, Chen Z, Yang X. et al. Increased 68Ga-FAPI Uptake in Chronic Cholecystitis and Degenerative Osteophyte. Clin Nucl Med 2021; 46: 601-602
• 31 Bentestuen M, Al-Obaydi N, Zacho HD. FAPI-avid nonmalignant PET/CT findings: An expedited systematic review. Semin Nucl Med 2023; 53: 694-705
• 32 Pabst KM, Kessler L, Ferdinandus J. et al. [68Ga]Ga-FAPI versus 2-[18F]FDG PET/CT in patients with autoimmune thyroiditis: a case control study. EJNMMI Res 2024; 14: 66
• 33 Kessler L, Ferdinandus J, Hirmas N. et al. Pitfalls and Common Findings in 68Ga-FAPI PET: A Pictorial Analysis. J Nucl Med 2022; 63: 890-896
• 34 Zhou Y, Yang X, Liu H. et al. Value of [68Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis. Eur J Nucl Med Mol Imaging 2021; 48: 3493-3501
• 35 Roberts EW, Deonarine A, Jones JO. et al. Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia. J Exp Med 2013; 210: 1137-1151