99mTc-FAPI SPECT/CT for predicting disease progression in fibrosing interstitial lung diseases: study protocol of a single-centre prospective cohort study.

INTRODUCTION

Fibrosing interstitial lung diseases (F-ILD) affect substantial patient populations with significant mortality and socioeconomic burden. Approximately one-third of patients with F-ILD develop a progressive fibrosing phenotype with poor outcomes. Current monitoring methods, including pulmonary function testing and high-resolution CT (HRCT), often lag behind increases in fibrotic activity, limiting early risk identification and optimal treatment timing. Fibroblast activation protein (FAP) imaging can capture fibrotic activity at the pathological level. This study aims to evaluate the incremental value of ⁹⁹ᵐTc-FAPI single-photon emission CT (SPECT)/CT for early warning of disease progression in F-ILD and develop a predictive model integrating fibroblast activation protein inhibitor (FAPI) quantitative parameters with clinical variables.

METHODS AND ANALYSIS: This prospective, single-centre, observational cohort study will recruit 380 adult patients with confirmed F-ILD diagnoses from December 2024 to June 2027, with 12-month follow-up. Comprehensive baseline evaluation includes pulmonary function testing, 6-min walk test, laboratory investigations and ⁹⁹ᵐTc-FAPI SPECT/CT imaging. Follow-up visits at 3, 6 and 12 months will assess clinical outcomes. The primary outcome is disease progression within 12 months, defined as ≥5% forced vital capacity decline, ≥10% diffusing capacity of the lungs for carbon monoxide decline, increased fibrosis on HRCT, acute exacerbation or death. Cox proportional hazards regression models will be used for predictive model construction, with internal validation using bootstrap resampling and temporal split methods.

ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of Fujian Provincial Hospital (K2024-11-010) and will be conducted according to the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications and academic conference presentations. De-identified individual participant data will be available upon reasonable request after primary publication.

TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry ChiCTR2400093808.