Clinical Application of 68Ga-1A12 PET in Fibrosis-related Diseases

Overview

Organ fibrosis is a common end-stage pathological change in various chronic diseases, characterized by excessive deposition of extracellular matrix (ECM) and disruption of tissue architecture, which can involve multiple organs such as the heart, liver, lungs, kidneys, and intestines. Although the pathogenic triggers vary, the core molecular mechanisms are highly conserved, involving sustained activation of signaling pathways such as transforming growth factor-β (TGF-β), transdifferentiation of fibroblasts into myofibroblasts, and processes like epithelial-mesenchymal transition (EMT) . Currently, histopathological biopsy remains the gold standard for the diagnosis and staging of fibrosis, but its inherent invasiveness, sampling errors, and procedural risks limit its repeated application and dynamic monitoring . In clinical practice, functional imaging modalities such as high-resolution computed tomography (CT) and ultrasonic elastography have been employed to assess fibrosis in specific organs (e.g., lungs, liver). However, these methods predominantly rely on secondary morphological or physical property alterations, exhibiting limited capacity for identifying early-stage, active molecular-level pathological processes. Additionally, they are challenging to perform for systemic, multi-target quantitative evaluation.

Organ fibrosis is a common end-stage pathological change in various chronic diseases, characterized by excessive deposition of extracellular matrix (ECM) and disruption of tissue architecture, which can involve multiple organs such as the heart, liver, lungs, kidneys, and intestines. Although the pathogenic triggers vary, the core molecular mechanisms are highly conserved, involving sustained activation of signaling pathways such as transforming growth factor-β (TGF-β), transdifferentiation of fibroblasts into myofibroblasts, and processes like epithelial-mesenchymal transition (EMT) . Currently, histopathological biopsy remains the gold standard for the diagnosis and staging of fibrosis, but its inherent invasiveness, sampling errors, and procedural risks limit its repeated application and dynamic monitoring . In clinical practice, functional imaging modalities such as high-resolution computed tomography (CT) and ultrasonic elastography have been employed to assess fibrosis in specific organs (e.g., lungs, liver). However, these methods predominantly rely on secondary morphological or physical property alterations, exhibiting limited capacity for identifying early-stage, active molecular-level pathological processes and posing challenges for systemic, multi-target quantitative evaluation . Positron Emission Tomography (PET), as a molecular imaging technique, enables non-invasive visualization of the distribution and concentration of specific biomolecules in vivo through radionuclide-labeled targeted probes, thereby reflecting the pathophysiological state of diseases \[4\]. In recent years, the development of novel PET probes targeting key fibrosis-related targets (e.g., fibroblast-activated protein, collagen) has become a research hotspot . Among these, the disc domain receptor, a tyrosine kinase receptor activated by collagen, exhibits significantly high expression in fibrotic tissues. Unlike the rapid and transient activation pattern of classical receptor tyrosine kinases (RTKs), the disc domain receptor demonstrates a slow and sustained phosphorylation characteristic ("slow-on slow-off") after binding to collagen. This property aligns well with its biological role in maintaining continuous signaling during chronic fibrosis . Therefore, molecular imaging probes targeting the disc domain receptor theoretically enable specific identification of active fibrotic lesions and reveal their molecular activity levels. 68Ga-1A12 is a PET imaging agent targeting the discoid domain receptor family. Preliminary studies have demonstrated its excellent targeting affinity in fibrosis models and certain clinical cases. Compared to conventional imaging that only reflects morphological changes, 68Ga-1A12 PET holds two major potential breakthroughs: first, the early detection of metabolically active fibrotic lesions before significant anatomical alterations occur; and second, the longitudinal and objective monitoring of fibrosis activity through semi-quantitative parameters such as Standardized Uptake Value (SUV), thereby providing a novel perspective for disease staging and therapeutic evaluation. However, there is currently a lack of prospective clinical evidence regarding the systemic diagnostic efficacy, differential value, and predictive capacity for therapeutic response of 68Ga-1A12 PET in human multi-organ fibrotic diseases. Clarifying its clinical application sensitivity, specificity, and prognostic relevance is an indispensable key step in advancing this technology from basic research to clinical translation. In conclusion, this study aims to systematically evaluate the clinical value of 68Ga-1A12 PET in identifying active lesions, differential diagnosis, and predicting anti-fibrotic efficacy in fibrosis-related diseases through a prospective clinical study, thereby providing high-level evidence-based medical support for the standardized application of this technology.