# Assessment of the Diagnostic Value of [68Ga]Ga-FAPI-04 and [18F]FDG PET in a PHMG-p-Induced Pulmonary Fibrosis Murine Model

## TL;DR

This study tests two PET imaging agents for detecting lung fibrosis in mice, showing that [68Ga]Ga-FAPI-04 is more effective than [18F]FDG.

## Contribution

Demonstrates [68Ga]Ga-FAPI-04 as a novel and sensitive PET tracer for pulmonary fibrosis in a PHMG-p-induced mouse model.

## Key findings

- [68Ga]Ga-FAPI-04 PET showed significantly higher lung uptake in fibrotic mice compared to controls.
- FAP expression was upregulated in PHMG-p-treated mice, supporting its role as a fibrosis biomarker.
- CT and histology confirmed increased fibrosis severity in PHMG-p-treated mice over time.

## Abstract

Background/Objectives: Pulmonary fibrosis is a progressive and fatal lung disease with limited diagnostic and therapeutic options. Fibroblast activation protein (FAP) has emerged as a promising molecular imaging target for the non-invasive assessment of fibrotic activity. This study aimed to evaluate the diagnostic feasibility of [68Ga]Ga-FAP inhibitor (FAPI) and [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) for imaging pulmonary fibrosis in a mouse model. Methods: A pulmonary fibrosis model was established by intratracheal administration of polyhexamethylene guanidine-phosphate (PHMG-p) to C57BL/6 mice. Fibrosis severity was quantified by the Ashcroft scoring system using hematoxylin and eosin and Masson’s trichrome staining and evaluated by computed tomography (CT) imaging at 7, 14, and 21 days after PHMG-p exposure. PET imaging was performed, and ex vivo biodistribution was assessed after injection of [68Ga]Ga-FAPI-04 and [18F]FDG. Results: Histological analysis and Ashcroft scoring revealed greater fibrosis severity in the PHMG-p-treated group. Western blot analysis demonstrated upregulation of FAP expression after PHMG-p exposure. CT showed increased mean lung density, while [68Ga]Ga-FAPI-04 PET revealed significantly elevated pulmonary uptake of [68Ga]Ga-FAPI-04 in the PHMG-p-treated group compared with the controls. [18F]FDG PET imaging also showed higher uptake of [18F]FDG in the PHMG-p-treated group than in the controls. Ex vivo biodistribution confirmed greater [68Ga]Ga-FAPI-04 accumulation in the lungs of PHMG-p-treated mice. Conclusions: [68Ga]Ga-FAPI-04 PET serves as a sensitive imaging biomarker for evaluation of fibrotic activity in PHMG-p-induced pulmonary fibrosis and complements [18F]FDG PET for assessing disease progression and therapeutic response.