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. 2025 Jul 22.
doi: 10.1007/s00259-025-07468-9. Online ahead of print.

From bench to bedside, blade, and back: FAP expression in juvenile angiofibroma. Potential implications for FAPI-PET/CT imaging and targeted therapy?

Lukas Pillong  1 , Caroline Burgard  2 , Florian Rosar  2 , Betül Demirkol  3 , Rafail Ebner  3 , Maximilian Linxweiler  3 , Alessandro Bozzato  3 , Bernhard Schick #  3 , Silke Wemmert #  3
Affiliations

From bench to bedside, blade, and back: FAP expression in juvenile angiofibroma. Potential implications for FAPI-PET/CT imaging and targeted therapy?

Lukas Pillong et al. Eur J Nucl Med Mol Imaging. .

Abstract

Purpose: Juvenile angiofibroma (JA) is a rare, benign fibrovascular tumor that predominantly affects adolescent males. The underlying biological mechanisms remain poorly understood. Fibroblast activation protein (FAP), known for its involvement in tumor invasion, matrix remodeling, and angiogenesis, has been implicated in various malignancies but has not been studied in JA so far.

Methods: We investigated FAP expression in JA samples (N = 19) using real-time (RT)-PCR (N = 10) and immunohistochemistry (N = 18). In addition, Vimentin and PECAM1/CD31 were analyzed to further characterize the tumor microenvironment. For one patient, preoperative FAPI-PET/CT imaging was conducted, and FAP expression was correlated with radiotracer uptake. Postoperative histopathological analyses of the excised tumor were performed to validate the imaging findings.

Results: We found consistent expression of FAP, Vimentin and PECAM1/CD31 in all JA analyzed by RT-PCR. Moreover, substantial intra-and intertumor heterogeneity in FAP protein expression was observed, ranging from negative up to strong positive areas. Vimentin and PECAM1/CD31 showed variable expression patterns consistent with the fibrovascular character of JA. FAPI-PET/CT imaging accurately identified the tumor, with radiotracer uptake closely matching the distribution of FAP expression observed histologically.

Conclusions: This study is the first demonstrating FAP expression in JA and validating its occurrence using FAPI-PET/CT imaging. The strong correlation between FAP expression and radiotracer uptake in FAPI-PET/CT highlights the potential of this imaging modality as a non-invasive diagnostic tool. This will improve diagnosis and is the basis for further investigations of FAP-targeted therapies for JA treatment.

Keywords: Epithelial-Mesenchymal Transition (EMT); FAPI-PET/CT; Fibroblast Activation Protein (FAP); Juvenile angiofibroma; Non-invasive imaging; Tumor biomarker.

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Conflict of interest statement

Declarations. Ethics approval/institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Saarland University (protocol code #218/10, approved on 16 December 2010). Consent to participate: Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Consent to publish: The authors affirm that human research participants provided informed consent to publish all data and images in this article. Conflicts of interest: The authors declare no conflicts of interest.

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