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

Sep 30, 2026

Upload by Jacob

Pulmonary fibrosis is a progressive, fatal lung disease with limited diagnostic and therapeutic options. Fibroblast activation protein (FAP) has emerged as a promising molecular imaging target for assessing fibrotic activity non-invasively. This study evaluates the diagnostic feasibility of [68Ga]Ga-FAP inhibitor (FAPI) and [18F]FDG PET to image pulmonary fibrosis in a mouse model, using histology, CT, and PET plus ex vivo biodistribution.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Introduction

Pulmonary fibrosis and diagnostic challenges

Molecular imaging approaches

FDG PET and its limitations

FAP/FAPI as an imaging target

Methods

Results

Conclusions

Article Assessment of the Diagnostic Value of [68 Ga]Ga-FAPI-04 and [18 F]FDG PET in a PHMG-p-Induced Pulmonary Fibrosis Murine Model So Young Kim 1,2,†, Jun Young Park 2,†, Ye Lim Cho 2 and Won Jun Kang 2, * Academic Editor: Davide Colombi Received: 24 November 2025 Revised: 11 December 2025 Accepted: 14 December 2025 Published: 19 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Nuclear Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Republic of Korea; [soykim@cauhs.or.kr](soykim@cauhs.or.kr) [2](2 Department of Nuclear Medicine)[ Department of Nuclear Medicine](2 Department of Nuclear Medicine), [Severance Hospital](Severance Hospital), [Yonsei University College of Medicine](Yonsei University College of Medicine), [50-1 Yonsei-ro](50-1 Yonsei-ro), Seodaemun-gu, Seoul 03722, Republic of Korea; [abies60@naver.com](abies60@naver.com) (J.Y.P.); [etommi@yuhs.ac](etommi@yuhs.ac) (Y.L.C.) * [Correspondence: mdkwj@yuhs.ac](Correspondence: mdkwj@yuhs.ac)[ ](Correspondence: mdkwj@yuhs.ac)† These authors contributed equally to this work. 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. Keywords: fibroblast activation protein; [68Ga]Ga-FAPI-04; [18F]FDG; positron emission tomography; pulmonary fibrosis 1. Introduction Pulmonary fibrosis is a subset of interstitial lung diseases characterized by excessive deposition of extracellular matrix and scarring of the lung parenchyma, leading to progressive loss of respiratory function. Although the underlying etiologies vary, the most common form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF), which has a poor prognosis, with five-year survival rates of 20–40%[1] . Treatment options for IPF are limited, and new therapeutic agents are currently under development [1–3] . Recently, new antifibrotic therapies such as nerandomilast have shown promising results in patients with IPF and progressive pulmonary fibrosis. These advances highlight the

FAQs

What is the main diagnostic goal of this study?

To assess the feasibility of using [68Ga]Ga-FAPI-04 PET and [18F]FDG PET for imaging pulmonary fibrosis in a PHMG-p-induced mouse model.

How was pulmonary fibrosis induced and quantified in the experiment?

Pulmonary fibrosis was induced by intratracheal PHMG-p administration in C57BL/6 mice, with fibrosis severity quantified using Ashcroft scoring from H&E and Masson’s trichrome staining, alongside CT imaging at multiple time points.

How did [68Ga]Ga-FAPI-04 PET performance compare with [18F]FDG PET?

[68Ga]Ga-FAPI-04 PET showed significantly increased pulmonary uptake in PHMG-p-treated mice, and ex vivo biodistribution confirmed greater lung accumulation, while [18F]FDG PET also demonstrated higher uptake in treated animals but is discussed as less specific for fibrotic remodeling.

Sep 30, 2026

Upload by Jacob