A Novel 68Ga-Labeled Integrin α4β7-Targeted Radiopharmaceutical for PET/CT Imaging of DSS-Induced Murine Colitis

Background: Inflammatory bowel diseases (IBD) rely on invasive methods for detecting intestinal inflammation, with the needs for non-invasive molecular imaging tools being unmet. Integrin α4β7 is a key target in IBD pathogenesis due to its role in the recruitment of T cells. This study aimed to develop a novel 68Ga-labeled integrin α4β7-targeted radiopharmaceutical (68Ga-A2) and evaluate its feasibility for non-invasive PET/CT imaging of IBD inflammation in a dextran sulfate sodium (DSS)-induced murine colitis model. Methods: 68Ga-A2 was synthesized via radiolabeling DOTA-A2 with 68Ga. In vitro properties (radiochemical purity, stability, binding specificity, and affinity) of 68Ga-A2 were validated. The DSS-induced colitis model was established and confirmed in C57BL/6J mice, followed by in vivo PET/CT imaging, ex vivo biodistribution studies, and histological (HE and IHC) analyses to evaluate the targeting efficacy of 68Ga-A2. Results: 68Ga-A2 was prepared efficiently (20 min) with a radiochemical purity of >95% and demonstrated good in vitro stability. It exhibited specific binding to integrin α4β7 with a Kd of 68.48 ± 6.55 nM. While whole-body PET/CT showed no visible inflammatory focus uptake, ex vivo imaging and biodistribution of colon tissue revealed significantly higher uptake in DSS-treated mice compared to that in healthy/blocking groups, which was consistent with histological evidence of inflammation. Conclusions: 68Ga-A2 demonstrated specific targeting of IBD inflammatory foci in vitro and ex vivo. Despite whole-body imaging limitations, further optimization of its structure may enable it to become a promising non-invasive PET agent for IBD. These findings support future clinical investigations to validate its utility in IBD diagnosis and monitoring.