Zachary T Rosenkrans1, Christopher F Massey1, Ksenija Bernau2, Carolina A Ferreira1, Justin J Jeffery3, Jefree J Schulte4, Melissa Moore5, Frank Valla5, Jeanine M Batterton1, Christopher R Drake5, Alan B McMillan1, Nathan Sandbo2, Ali Pirasteh6,7, Reinier Hernandez8,9,10. 1. Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Room 7137, WI, 53705, Madison, USA. 2. Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA. 3. University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA. 4. Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA. 5. SOFIE, Dulles, VA, USA. 6. Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Room 7137, WI, 53705, Madison, USA. Pirasteh@wisc.edu. 7. Department of Radiology, University of Wisconsin-Madison, 1111 Highland Ave., Room 2423, WI, 53705, Madison, USA. Pirasteh@wisc.edu. 8. Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Room 7137, WI, 53705, Madison, USA. Hernandez6@wisc.edu. 9. University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA. Hernandez6@wisc.edu. 10. Department of Radiology, University of Wisconsin-Madison, 1111 Highland Ave., Room 2423, WI, 53705, Madison, USA. Hernandez6@wisc.edu.
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.
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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