Molecular Imaging of Fibroblast Activation Protein in Response to Cardiac Injury Using [<sup>68</sup>Ga]Ga-DATA<sup>5m</sup>.SA.FAPi

Molecular Imaging of Fibroblast Activation Protein in Response to Cardiac Injury Using [<sup>68</sup>Ga]Ga-DATA<sup>5m</sup>.SA.FAPi

<b>Background/Objectives:</b> Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [<sup>68</sup>Ga]Ga-DATA<sup>5m</sup>.SA.FAP...

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Main Authors: Victoria Weissenböck, Lukas Weber, Michaela Schlederer, Laura Silva Sousa, Anna Stampfer, Simge Baydar, Thomas Nakuz, Raffaella Calabretta, Ana Isabel Antunes Goncalves, Xiang Li, Frank Rösch, Bruno K. Podesser, Lukas Kenner, Marcus Hacker, Attila Kiss, Cecile Philippe
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceuticals
Subjects:
FAP
FAPI tracer
cardiac fibrosis
PET
Online Access:https://www.mdpi.com/1424-8247/18/5/658
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Summary:<b>Background/Objectives:</b> Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [<sup>68</sup>Ga]Ga-DATA<sup>5m</sup>.SA.FAPi for PET imaging of replacement fibrosis following myocardial infarction (MI) or interstitial fibrosis associated with hypertrophy. <b>Methods</b>: MI or transverse aortic constriction (TAC)-induced hypertrophy was induced in C57BL/6 mice, with sham-operated animals serving as controls. At multiple time points during disease progression (1, 2, and 6 weeks post-surgery), [<sup>68</sup>Ga]Ga-DATA<sup>5m</sup>.SA.FAPi PET/CT scans were performed, followed by ex vivo investigations. Additionally, in vitro cell uptake experiments simulating hypertrophy were conducted. <b>Results</b>: Cardiac uptake of [<sup>68</sup>Ga]Ga-DATA5m.SA.FAPi significantly increased two weeks after MI induction (MI: 2.1 ± 0.2%ID/g, <i>n</i> = 7 vs. SHAM: 1.1 ± 0.2%ID/g, <i>n</i> = 5; <i>p</i> = 0.002), confirmed by ex vivo autoradiography. No significant difference was observed at six weeks post-MI (MI: 1.1 ± 0.1%ID/g, <i>n</i> = 4 vs. SHAM: 0.8 ± 0.0%ID/g, <i>n</i> = 3), indicating infarct healing completion. In contrast, TAC mice showed increased uptake after six weeks (TAC: 1.8 ± 0.2%ID/g, <i>n</i> = 6; <i>p</i> = 0.007), related to interstitial fibrosis progression. Consistently, high-stretched cardiac fibroblasts demonstrated a higher uptake compared to low-stretched conditioned ones, suggesting the stretch mediates regulation of FAP. <b>Conclusions</b>: This study demonstrated the efficacy of [<sup>68</sup>Ga]Ga-DATA<sup>5m</sup>.SA.FAPi for longitudinal imaging of cardiac fibrosis in response to different cardiac injuries. In vivo FAP imaging during cardiac remodeling may serve as a valuable tool for diagnosing and predicting disease progression, ultimately aiding in the clinical management of patients.
ISSN:1424-8247

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