⁶⁸Ga-citrate visualization study on ferroptosis through transferrin receptor 1 in periodontitis

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Periodontology

Background:

• Periodontitis leads to alveolar bone loss, a process linked to ferroptosis mediated by Transferrin Receptor 1 (TfR1).
• Non-invasive imaging of ferroptosis and periodontal remodeling is crucial for understanding disease progression.

Purpose of the Study:

• To investigate the utility of gallium-68 citrate (⁶⁸Ga-citrate) PET/CT for non-invasive imaging of ferroptosis and periodontal remodeling in vivo.
• To assess the correlation between TfR1 expression and ⁶⁸Ga-citrate uptake in an in vitro model of periodontitis.

Main Methods:

• In vitro studies used MC3T3-E1 cells stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS) to model inflammation and analyzed ferroptosis markers.
• In vivo studies utilized a ligature-induced periodontitis rat model, evaluating periodontal inflammation and bone metabolism with ⁶⁸Ga-citrate, ¹⁸F-FDG, ¹⁸F-NaF PET/CT, and micro-CT.
• TfR1 expression and ⁶⁸Ga-citrate uptake were correlated using cellular assays and TfR1 knockdown.

Main Results:

• LPS stimulation in vitro decreased cell viability, upregulated TfR1 and IL1β, and downregulated GPX4, with ⁶⁸Ga-citrate uptake positively correlating with TfR1 expression.
• In vivo, ⁶⁸Ga-citrate uptake increased in periodontal lesions over time, correlating with TfR1 upregulation and bone resorption.
• Minocycline treatment reduced TfR1 expression and ⁶⁸Ga-citrate uptake, while ¹⁸F-FDG and ¹⁸F-NaF confirmed inflammation and impaired calcium metabolism.

Conclusions:

• ⁶⁸Ga-citrate uptake is elevated in osteoblasts under inflammatory conditions and in periodontitis models, consistent with TfR1 expression.
• ⁶⁸Ga-citrate PET/CT imaging can non-invasively reflect ferroptosis-associated molecular changes by targeting TfR1.
• This imaging approach holds potential for monitoring periodontal disease and therapeutic responses.