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

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

doi:10.1007/s00259-022-05814-9

Cited by 45 publications

(45 citation statements)

References 60 publications

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“…Recently, it was demonstrated that fibroblast activation protein inhibitor (FAPI), which was used for cancer imaging, could monitor and evaluate therapeutic effect in interstitial lung disease (ILD), especially IPF in a clinical study. It is confirmed that the [ 68 Ga]Ga-FAPI-46 lung uptake in the BM mice group at 14 days was decreased compared with that at 7 days . Therefore, it is possible to diagnose early pulmonary fibrosis activity.…”

Section: Discussionmentioning

confidence: 55%

“…It is confirmed that the [ 68 Ga]Ga-FAPI-46 lung uptake in the BM mice group at 14 days was decreased compared with that at 7 days. 56 Therefore, it is possible to diagnose early pulmonary fibrosis activity. However, unlike [ 68 Ga]Ga-FAPI-46, we focused on detecting the early stage of pulmonary fibrosis of lung cancer patients who received radiation therapy.…”

Section: ■ Discussionmentioning

confidence: 99%

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Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging

et al. 2022

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Early diagnosis of radiation-induced pulmonary fibrosis (RIPF) in lung cancer patients after radiation therapy is important. A gastrin-releasing peptide receptor (GRPR) mediates the inflammation and fibrosis after irradiation in mice lungs. Previously, our group synthesized a GRPR-targeted positron emission tomography (PET) imaging probe, [ 64 Cu]Cu-NODA-GA-galacto-bombesin (BBN), an analogue peptide of GRP. In this study, we evaluated the usefulness of [ 64 Cu]Cu-NODAGA-galacto-BBN for the early prediction of RIPF. We prepared RIPF mice and acquired PET/CT images of [ 18 F]F-FDG and [ 64 Cu]Cu-NODAGA-galacto-BBN at 0, 2, 5, and 11 weeks after irradiation (n = 3−10). We confirmed that [ 64 Cu]Cu-NODAGA-galacto-BBN targets GRPR in irradiated RAW 264.7 cells. In addition, we examined whether [ 64 Cu]Cu-NODAGA-galacto-BBN monitors the therapeutic efficacy in RIPF mice (n = 4). As a result, the lung uptake ratio (irradiated-to-normal) of [ 64 Cu]Cu-NODAGA-galacto-BBN was the highest at 2 weeks, followed by its decrease at 5 and 11 weeks after irradiation, which matched with the expression of GRPR and was more accurately predicted than [ 18 F]F-FDG. These uptake results were also confirmed by the cell uptake assay. Furthermore, [ 64 Cu]Cu-NODAGA-galacto-BBN could monitor the therapeutic efficacy of pirfenidone in RIPF mice. We conclude that [ 64 Cu]Cu-NODAGA-galacto-BBN is a novel PET imaging probe for the early prediction of RIPF-targeting GRPR expressed during the inflammatory response.

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Section: Discussionmentioning

confidence: 55%

Section: ■ Discussionmentioning

confidence: 99%

Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging

et al. 2022

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“…Previous studies characterized FAPI uptake in other fibrotic organ changes such as the lung: In a proof-of-concept study, we recently demonstrated increased pulmonary [ 68 Ga] Ga-FAPI-04 uptake in patients with SSc-related interstitial lung disease at risk of progression and that increased [ 68 Ga] Ga-FAPI-04 uptake at baseline is associated with the deterioration of lung function on follow-up [16]. Other studies characterized the role of FAPI-PET CT in idiopathic pulmonary fibrosis [21,22]. As limitation of this study, the patient number is too small to apply advanced statistical models for the analysis of the association of [ 68 Ga]Ga-FAPI-04 uptake with the course of myocardial fibrosis.…”

Section: Discussionmentioning

confidence: 97%

Assessment of myocardial fibrosis in patients with systemic sclerosis using [68Ga]Ga-FAPI-04-PET-CT

Treutlein,

Distler,

Tascilar

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose Myocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization of fibroblast activation as early readout of MF has not been feasible to date. Here, we characterize 68Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([68Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF. Methods In this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [68Ga]Ga-FAPI-04-PET-CT and cardiac MRI (cMRI) and clinical and serologic investigations just before baseline and during follow-up between January 2020 and December 2020. Myocardial biopsy was performed as clinically indicated. Results [68Ga]Ga-FAPI-04 tracer uptake was increased in SSc-related MF with higher uptake in SSc patients with arrhythmias, elevated serum-NT-pro-BNP, and increased late gadolinium enhancement (LGE) in cMRI. Histologically, myocardial biopsies from cMRI- and [68Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP+ fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [68Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [68Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [68Ga]Ga-FAPI-04 uptake associated with changes in the activity of SSc-related MF, while cMRI parameters remained stable after regression of molecular activity and rather indicated tissue damage. Conclusions We present first in-human evidence that [68Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.

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“…Rosenkrans et al evaluated the lung uptake of [ 68 Ga]FAPI-46 in a mouse bleomycin model and observed a higher and signi cant lung uptake of the radiotracer at 7 and 14 days with the highest uptake seen at day 14 [25]. Another study successfully used [ 68 Ga]FAPI-46 to discriminate lesions of lung carcinoma and lung brosis in ILD patients [19].…”

Section: Discussionmentioning

confidence: 99%

Usefulness of FAPα assessment in bronchoalveolar lavage as a marker of fibrogenesis: results of a preclinical study and first report in patients with idiopathic pulmonary fibrosis

Lavis

Pingitore

Doumont

et al. 2023

Preprint

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Background: Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis. Methods: The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF). Results: Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPa levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels. Conclusions: Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAP in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease.

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

Cited by 45 publications

References 60 publications

Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging

Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging

Assessment of myocardial fibrosis in patients with systemic sclerosis using [68Ga]Ga-FAPI-04-PET-CT

Usefulness of FAPα assessment in bronchoalveolar lavage as a marker of fibrogenesis: results of a preclinical study and first report in patients with idiopathic pulmonary fibrosis

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