68Ga-FAPi: Pathways and Diagnosis in Cardiac Imaging

Hamson EJ, Keane FM, Tholen S, Schilling O, Gorrell MD. Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteomics Clin Appl. 2014;8(5–6):454–63. https://doi.org/10.1002/prca.201300095.

Article  CAS  PubMed  Google Scholar 

Brilla CG. Renin-angiotensin-aldosterone system and myocardial fibrosis. Cardiovasc Res. 2000;47(1):1–3. https://doi.org/10.1016/s0008-6363(00)00092-4.

Article  CAS  PubMed  Google Scholar 

Sidrak MMA, De Feo MS, Corica F, Gorica J, Conte M, Filippi L, et al. Fibroblast activation protein inhibitor (FAPI)-based theranostics-where we are at and where we are heading: a systematic review. Int J Mol Sci. 2023;24(4):3863. https://doi.org/10.3390/ijms24043863. This is a recent Review paper on the theranostic potential of FAPI imaging.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18(2):99–115. https://doi.org/10.1038/s41573-018-0004-1.

Article  CAS  PubMed  Google Scholar 

Cheng JD, Dunbrack RL, Valianou M, Rogatko A, Alpaugh RK, Weiner LM. Promotion of tumor growth by murine fibroblast activation protein, a serine protease, in an animal model. Cancer Res. 2002;62(16):4767–72.

CAS  PubMed  Google Scholar 

Santos AM, Jung J, Aziz N, Kissil JL, Puré E. Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. J Clin Invest. 2009;119(12):3613–25. https://doi.org/10.1172/JCI38988.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Siebermair J, Köhler MI, Kupusovic J, Nekolla SG, Kessler L, Ferdinandus J, et al. Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling. J Nucl Cardiol. 2021;28(3):812–21. https://doi.org/10.1007/s12350-020-02307-w.

Article  CAS  PubMed  Google Scholar 

Iking J, Staniszewska M, Kessler L, Klose JM, Lückerath K, Fendler WP, et al. Imaging inflammation with positron emission tomography. Biomedicines. 2021;9(2):212. https://doi.org/10.3390/biomedicines9020212.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bengel FM, Ross TL. Emerging imaging targets for infiltrative cardiomyopathy: inflammation and fibrosis. J Nucl Cardiol. 2019;26(1):208–16. https://doi.org/10.1007/s12350-018-1356-y.

Article  PubMed  Google Scholar 

Prabhu SD, Frangogiannis NG. The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. Circ Res. 2016;119(1):91–112. https://doi.org/10.1161/CIRCRESAHA.116.303577.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kain V, Prabhu SD, Halade GV. Inflammation revisited: inflammation versus resolution of inflammation following myocardial infarction. Basic Res Cardiol. 2014;109(6):444. https://doi.org/10.1007/s00395-014-0444-7.

Article  CAS  PubMed  Google Scholar 

Kempf T, Zarbock A, Vestweber D, Wollert KC. Anti-inflammatory mechanisms and therapeutic opportunities in myocardial infarct healing. J Mol Med (Berl). 2012;90(4):361–9. https://doi.org/10.1007/s00109-011-0847-y.

Article  PubMed  Google Scholar 

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(9):e010628. https://doi.org/10.1161/CIRCIMAGING.120.010628. This is an important paper demonstrating the correlation between cardiovascular diseases and FAPI uptake.

Article  PubMed  PubMed Central  Google Scholar 

Lyu Z, Han W, Zhao H, Jiao Y, Xu P, Wang Y, et al. A clinical study on relationship between visualization of cardiac fibroblast activation protein activity by Al18F-NOTA-FAPI-04 positron emission tomography and cardiovascular disease. Front Cardiovasc Med. 2022;9:921724. https://doi.org/10.3389/fcvm.2022.921724. In this paper, further evidence are reported for a correlation between FAPI uptake and cardiovascular diseases.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Varasteh Z, Mohanta S, Robu S, Braeuer M, Li Y, Omidvari N, et al. Molecular imaging of fibroblast activity after myocardial infarction using a 68Ga-labeled fibroblast activation protein inhibitor, FAPI-04. J Nucl Med. 2019;60(12):1743–9. https://doi.org/10.2967/jnumed.119.226993.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Langer LBN, Hess A, Korkmaz Z, Tillmanns J, Reffert LM, Bankstahl JP, et al. Molecular imaging of fibroblast activation protein after myocardial infarction using the novel radiotracer [68Ga]MHLL1. Theranostics. 2021;11(16):7755–66. https://doi.org/10.7150/thno.51419.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xie B, Wang J, Xi XY, Guo X, Chen BX, Li L, et al. Fibroblast activation protein imaging in reperfused ST-elevation myocardial infarction: comparison with cardiac magnetic resonance imaging. Eur J Nucl Med Mol Imaging. 2022;49(8):2786–97. https://doi.org/10.1007/s00259-021-05674-9. This is a very important paper, highlighting the correlation between post-infarction scar and FAPI uptake, which is related to reparative processes exceeding the extent of myocardial scar.

Article  CAS  PubMed  Google Scholar 

Diekmann J, Koenig T, Zwadlo C, Derlin T, Neuser J, Thackeray JT, et al. Molecular imaging identifies fibroblast activation beyond the infarct region after acute myocardial infarction. J Am Coll Cardiol. 2021;77(14):1835–7. https://doi.org/10.1016/j.jacc.2021.02.019. Also in this paper, there is evidence that the area affected by reparative processes after myocardial infarction exceeds that of myocardial scar.

Article  CAS  PubMed  Google Scholar 

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. 2022;29(5):2254–61. https://doi.org/10.1007/s12350-021-02603-z.

Article  PubMed  Google Scholar 

Kessler L, Kupusovic J, Ferdinandus J, Hirmas N, Umutlu L, Zarrad F, et al. Visualization of fibroblast activation after myocardial infarction using 68Ga-FAPI PET. Clin Nucl Med. 2021;46(10):807–13. https://doi.org/10.1097/RLU.0000000000003745. In this paper, a correlation between markers of cardiac injury and FAPI uptake is shown.

Article  Google Scholar 

Qiao P, Wang Y, Zhu K, Zheng D, Song Y, Jiang D, et al. Noninvasive monitoring of reparative fibrosis after myocardial infarction in rats using 68Ga-FAPI-04 PET/CT. Mol Pharm. 2022;19(11):4171–8. https://doi.org/10.1021/acs.molpharmaceut.2c00551.

Article  CAS  Google Scholar 

Caobelli F, Nappi C. A spotlight on fibroblast-activated protein inhibitor (FAPi) cardiovascular imaging. Clin Transl Imaging. 2023. https://doi.org/10.1007/s40336-023-00548-6.

Article  Google Scholar 

Wang G, Yang Q, Wu S, Xu X, Li X, Liang S, et al. Molecular imaging of fibroblast activity in pressure overload heart failure using [68 Ga]Ga-FAPI-04 PET/CT. Eur J Nucl Med Mol Imaging. 2023;50(2):465–74. https://doi.org/10.1007/s00259-022-05984-6.

Article  CAS  PubMed  Google Scholar 

Song W, Zhang X, He S, Gai Y, Qin C, Hu F, et al. 68Ga-FAPI PET visualize heart failure: from mechanism to clinic. Eur J Nucl Med Mol Imaging. 2023;50(2):475–85. https://doi.org/10.1007/s00259-022-05994-4.

Article  CAS  PubMed  Google Scholar 

Wang L, Zhang Z, Zhao Z, Yan C, Fang W. 68Ga-FAPI right heart uptake in a patient with idiopathic pulmonary arterial hypertension. J Nucl Cardiol. 2022;29(3):1475–7. https://doi.org/10.1007/s12350-020-02407-7.

Article  PubMed  Google Scholar 

Xing H-Q, Gong J-N, Chen B-X, Guo X-J, Yang Y-H, Huo L, et al. Comparison of 68Ga-FAPI imaging and cardiac magnetic resonance in detection of myocardial fibrosis in a patient with chronic thromboembolic pulmonary hypertension. J Nucl Cardiol. 2022;29(5):2728–30. https://doi.org/10.1007/s12350-020-02517-2.

Article  PubMed  Google Scholar 

Chen BX, Xing HQ, Gong JN, Guo XJ, Xi XY, Yang YH, et al. Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension. Eur J Nucl Med Mol Imaging. 2022;49(4):1211–22. https://doi.org/10.1007/s00259-021-05577-9.

Article  CAS  PubMed  Google Scholar 

Gu Y, Han K, Zhang Z, Zhao Z, Yan C, Wang L, et al. 68Ga-FAPI PET/CT for molecular assessment of fibroblast activation in right heart in pulmonary arterial hypertension: a single-center, pilot study. J Nucl Cardiol. 2023;30(2):495–503. https://doi.org/10.1007/s12350-022-02952-3.

Article  PubMed  Google Scholar 

Niu N, Huo L, Zhang S, Liu Y, Li X. Immune checkpoint inhibitor-associated cardiotoxicity detected by 68Ga-DOTATATE PET/CT and 68Ga-FAPI PET/CT. Eur Heart J Cardiovasc Imaging. 2022;23(3):e123. https://doi.org/10.1093/ehjci/jeab189. This paper highlights the potential role of FAPI to predict inflammatory cardiac alterations in patients under therapy with immune checkpoint inhibitors.

Article  PubMed  Google Scholar 

Totzeck M, Siebermair J, Rassaf T, Rischpler C. Cardiac fibroblast activation detected by positron emission tomography/computed tomography as a possible sign of cardiotoxicity. Eur Heart J. 2020;41(9):1060. https://doi.org/10.1093/eurheartj/ehz736.

Article  PubMed  Google Scholar 

Wei Y, Sun Y, Liu J, Zhang G, Qin X, Xu S, et al. Early detection of radiation-induced myocardial damage by [18F]AlF-NOTA-FAPI-04 PET/CT imaging. Eur J Nucl Med Mol Imaging. 2023;50(2):453–64. https://doi.org/10.1007/s00259-022-05962-y.

Article  CAS  PubMed  Google Scholar 

Wang L, Wang Y, Wang J, Xiao M, Xi XY, Chen BX, et al. Myocardial activity at 18F-FAPI PET/CT and risk for sudden cardiac death in hypertrophic cardiomyopathy. Radiology. 2023;306(2):e221052. https://doi.org/10.1148/radiol.221052.

Article  PubMed  Google Scholar 

Lin K, Chen X, Xue Q, Yao S, Miao W. Diffuse uptake of [68Ga]Ga-FAPI in the left heart

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