Abstract
Aortic aneurysm (AA) is a disease where aortic wall loses its elasticity, showing fibrosis. Fibroblast activation protein (FAP) expression can be evaluated using radiolabeled FAP-inhibitor (FAPI) PET in fibrosis. We investigated FAP expression in AA and the feasibility of 68Ga-FAPI PET for AA imaging. Twenty AA patients who were planned for resection were prospectively enrolled. Nine lung cancer patients were used as control. Markers including FAP expression were assessed in AA and the remote aorta. Preoperative 68Ga-FAPI-46 PET was evaluated visually and quantitatively using maximal standard uptake value (SUVmax), and were compared with the growth rate of AA. FAP expression was increased in Western blotting (P = 0.014), both in intima and adventitia of AA. The SUVmax was significantly correlated with the FAP expression (r = 0.678, P = 0.008). The SUVmax of AA was significantly higher than the aortic SUVmax of the control (P = 0.018). The growth rate of AA was different between the uptake grade groups (P = 0.029), and correlated with SUVmax (r = 0.625, P = 0.013). FAP expression is variably increased in AA and possibly related to the progression of AA. 68Ga-FAPI PET can be a promising imaging for evaluating FAP expression of AA.
Data availability
The datasets used in this study are available from the corresponding authors on reasonable request.
Abbreviations
- AA:
-
Aortic aneurysm
- CT:
-
Computed tomography
- FAP:
-
Fibroblast activation protein
- FAPI:
-
Fibroblast activation protein inhibitor
- IHC:
-
Immunohistochemistry
- MRI:
-
Magnetic resonance imaging
- PET:
-
Positron emission tomography
- SMA:
-
Smooth muscle actin
- SUV:
-
Standardized uptake value
- TGF:
-
Transforming growth factor
References
Braverman, A. C. et al. Braunwald’s heart disease: a textbook of cardiovascular medicine. (eds Douglas P, Zipes) 1295–1327 (Elsvier, 2018).
Fleming, C., Whitlock, E. P., Beil, T. L. & Lederle, F. A. Screening for abdominal aortic aneurysm: a best-evidence systematic review for the US Preventive Services Task Force. Ann. Int. Med. 142, 203–211 (2005).
Gao, J. et al. The mechanism and therapy of aortic aneurysms. Signal. Transduct. Target. Ther. 8, 55 (2023).
Wanhainen, A. et al. Editor (eds) ‘s choice European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms. Eur. J. Vasc Endovasc Surg. 57 8–93 (2019).
Quintana, R. A. & Taylor, W. R. Cellular mechanisms of aortic aneurysm formation. Circ. Res. 124, 607–618 (2019).
Mackay, C. D., Jadli, A. S., Fedak, P. W. & Patel, V. B. Adventitial fibroblasts in aortic aneurysm: unraveling pathogenic contributions to vascular disease. Diagnostics 12, 871 (2022).
Stenmark, K. R. et al. The adventitia: essential regulator of vascular wall structure and function. Annu. Rev. Physiol. 75, 23–47 (2013).
Gibb, A. A., Lazaropoulos, M. P. & Elrod, J. W. Myofibroblasts and fibrosis: mitochondrial and metabolic control of cellular differentiation. Circ. Res. 127, 427–447 (2020).
Niestrawska, J. A. et al. The role of tissue remodeling in mechanics and pathogenesis of abdominal aortic aneurysms. Acta Biomater. 88, 149–161 (2019).
Heo, G. S., Lou, L., Sultan, D. & Liu, Y. The latest advances in imaging crosstalk between the immune system and fibrosis in cardiovascular disease. J. Nucl. Med. 62, 1341–1346 (2021).
Mori, Y. et al. FAPI PET: fibroblast activation protein inhibitor use in oncologic and nononcologic disease. Radiology 306, e220749 (2023).
Kent, K. C. et al. Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. J. Vasc Surg. 52, 539–548 (2010).
Schuster, R., Rockel, J. S., Kapoor, M. & Hinz, B. The inflammatory speech of fibroblasts. Immunol. Rev. 302, 126–146. https://doi.org/10.1111/imr.12971 (2021).
Golledge, J. Abdominal aortic aneurysm: update on pathogenesis and medical treatments. Nat. Rev. Cardiol. 16, 225–242. https://doi.org/10.1038/s41569-018-0114-9 (2019).
Loktev, A. et al. A tumor-imaging method targeting cancer-associated fibroblasts. J. Nucl. Med. 59, 1423–1429 (2018).
Liu, F. et al. Fibroblast activation protein overexpression and clinical implications in solid tumors: a meta-analysis. PLoS One. 10, e0116683 (2015).
Fitzgerald, A. A. & Weiner, L. M. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev. 39, 783–803 (2020).
Dendl, K. et al. FAP and FAPI-PET/CT in malignant and non-malignant diseases: a perfect symbiosis? Cancers 13, 4946 (2021).
Brokopp, C. E. et al. Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata. Eur. Heart J. 32, 2713–2722 (2011).
Notohamiprodjo, S. et al. Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04. J Nucl. Cardiol. 1–8 (2021).
Song, W. et al. 68)Ga-FAPI PET visualize heart failure: from mechanism to clinic. Eur. J. Nucl. Med. Mol. Imaging. 50, 475–485. https://doi.org/10.1007/s00259-022-05994-4 (2023).
Byun, J. W. et al. Evaluation of fibroblast activation protein expression using (68)Ga-FAPI46 PET in hypertension-induced tissue changes. J. Nucl. Med. 65, 1776–1781. https://doi.org/10.2967/jnumed.124.267489 (2024).
Tingting, T. et al. The TGF-β pathway plays a key role in aortic aneurysms. Clin. Chim. Acta. 501, 222–228. https://doi.org/10.1016/j.cca.2019.10.042 (2020).
Gomez, D. et al. Syndromic and non-syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway. J. Pathol. 218, 131–142. https://doi.org/10.1002/path.2516 (2009).
Ailawadi, G. et al. Smooth muscle phenotypic modulation is an early event in aortic aneurysms. J. Thorac. Cardiovasc. Surg. 138, 1392–1399. https://doi.org/10.1016/j.jtcvs.2009.07.075 (2009).
Hu, C. et al. Fibroblast activation protein acts as a biomarker for monitoring ECM remodeling during aortic aneurysm via (68)Ga-FAPI-04 PET imaging. Adv. Sci. (Weinh). 12, e2411152. https://doi.org/10.1002/advs.202411152 (2025).
Acknowledgements
We would like to thank all participants for the contribution to this study. We would also like to thank all the study nurses and technical assistants for their study support.
Funding
This research was supported by a grant of the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (RS-2024-00350443 to J.C.P.).
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JCP and JWC designed the study. JWC and JWB acquired data. HYS and JCP analyzed data and drafted the manuscript. SPL and JWC participated in discussion and revision. All authors read and approved the final manuscript.
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All the proceduring during this study was approved by the Institutional Review Board of the Seoul National University Hospital (IRB No. 2207-016-1338) in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards, and informed consents were obtained from all the patients.
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Suh, H.Y., Byun, J.W., Lee, SP. et al. Feasibility of 68Ga-FAPI-46 PET for evaluating active fibrosis in aortic aneurysm. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44481-w
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DOI: https://doi.org/10.1038/s41598-026-44481-w
