FAPI Tracer en Vogue: Evaluating [68Ga]Ga-DATA5m.SA.FAPi for Molecular Imaging of Pulmonary Fibrosis

TL;DR

This study tests a new imaging agent for detecting lung fibrosis in mice and finds it shows promise for early detection.

Contribution

The novel contribution is evaluating [68Ga]Ga-DATA5m.SA.FAPi as a molecular imaging agent for pulmonary fibrosis in two mouse models.

Findings

Pulmonary tracer uptake increased in BLM mice as early as 5 weeks compared to controls.

Ex vivo analysis confirmed higher tracer uptake in BLM mice compared to controls.

FAP expression was elevated in early and mild disease stages but tracer uptake was higher in later stages.

Abstract

Background/Objectives: Radiolabeled fibroblast activation protein inhibitors (FAPIs) are emerging as promising imaging agents assessing fibrotic diseases. This study evaluates [68Ga]Ga-DATA5m.SA.FAPi for imaging pulmonary fibrosis in two mouse models, bleomycin-induced (BLM) and a transgenic (fra-2tg) model, both displaying characteristics of human pulmonary fibrotic diseases. Methods: In the BLM model, C57BL/6 mice were treated with bleomycin or isotonic sodium chloride (controls) for 4, 5, and 6 weeks, followed by [68Ga]Ga-DATA5m.SA.FAPi PET/CT scans. Fra-2tg mice and wildtype (WT) littermates underwent at 7, 11, and 18/19 weeks of age a PET/CT scan. The selected timepoints correspond to early, middle, and late disease stages for each model. Imaging was complemented by ex vivo quantification, histological, and immunohistochemical (IHC) analyses. Results: In BLM mice, pulmonary [68Ga]Ga-DATA5m.SA.FAPi uptake showed a trend toward increase as early as 5 weeks of treatment compared with the controls, which was confirmed by ex vivo analysis (BLM: 3.31 ± 0.29%ID/g, n = 5; control: 1.61 ± 0.29%ID/g, n = 4; p = 0.0035). In fra-2tg mice, no significant differences could be detected. IHC revealed elevated pulmonary FAP expression specifically at early (BLM) and mild (fra-2tg) disease stages, whereas for BLM, tracer uptake was more pronounced at later stages. Conclusions: Our findings complement and extend observations from previous studies and support the potential of FAPI tracers as molecular imaging agents for pulmonary fibrosis.

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