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European Journal of Nuclear Medicine and Molecular Imaging

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12.05.2022 | Original Article

[⁶⁸ Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity

verfasst von: Zachary T. Rosenkrans, Christopher F. Massey, Ksenija Bernau, Carolina A. Ferreira, Justin J. Jeffery, Jefree J. Schulte, Melissa Moore, Frank Valla, Jeanine M. Batterton, Christopher R. Drake, Alan B. McMillan, Nathan Sandbo, Ali Pirasteh, Reinier Hernandez

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 11/2022

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Abstract

Purpose

The lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis.

Methods

Pulmonary fibrosis was induced by intratracheal administration of bleomycin (1 U/kg) while intratracheal saline was administered to control mice. Subgroups from each cohort (n = 3–5) underwent dynamic 1 h PET/CT after intravenously injecting FAPI-46 radiolabeled with gallium-68 ([⁶⁸ Ga]Ga-FAPI-46) at 7 days and 14 days following disease induction. Animals were sacrificed following imaging for ex vivo gamma counting and histologic correlation. [⁶⁸ Ga]Ga-FAPI-46 uptake was quantified and reported as percent injected activity per cc (%IA/cc) or percent injected activity (%IA). Lung CT density in Hounsfield units (HU) was also correlated with histologic examinations of lung fibrosis.

Results

CT only detected differences in the fibrotic response at 14 days post-bleomycin administration. [⁶⁸ Ga]Ga-FAPI-46 lung uptake was significantly higher in the bleomycin group than in control subjects at 7 days and 14 days. Significantly (P = 0.0012) increased [⁶⁸ Ga]Ga-FAPI-46 lung uptake in the bleomycin groups at 14 days (1.01 ± 0.12%IA/cc) vs. 7 days (0.33 ± 0.09%IA/cc) at 60 min post-injection of the tracer was observed. These findings were consistent with an increase in both fibrinogenesis and FAP expression as seen in histology.

Conclusion

CT was unable to assess disease activity in a murine model of IPF. Conversely, FAPI PET detected both the presence and activity of lung fibrogenesis, making it a promising tool for assessing early disease activity and evaluating the efficacy of therapeutic interventions in lung fibrosis patients.

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Titel: [68 Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity
verfasst von: Zachary T. Rosenkrans
Christopher F. Massey
Ksenija Bernau
Carolina A. Ferreira
Justin J. Jeffery
Jefree J. Schulte
Melissa Moore
Frank Valla
Jeanine M. Batterton
Christopher R. Drake
Alan B. McMillan
Nathan Sandbo
Ali Pirasteh
Reinier Hernandez
Publikationsdatum: 12.05.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 11/2022
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05814-9

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[⁶⁸ Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity

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