Introduction & Objective: Autopsy studies in individuals with T1D demonstrated residual β cells. There are significant challenges in accurately evaluating in vivo insulin secretion from functional β-cells, hampering therapeutic translations of β-cell regeneration to human. Zn2+ is an excellent biomarker of β-cell insulin release. Tracking pancreatic free Zn2+ could provide a window to detect β-cell function. We aimed to investigate if a chelating-zinc PET probe could detect Zn2+ released from β-cells to evaluate their insulin secretion.
Methods: 18F-labeled Tripicolylamine (TPA) demonstrated high specific affinity to Zn2+. We evaluated 18F-TPA PET imaging in two mice models with/without glucose stimulation: in vivo healthy NODscid mice and ex vivo STZ-induced diabetic mice. Following PET imaging, biodistribution and immunostaining were conducted and analyzed.
Results: 18F-TPA PET imaging could efficiently detect change in healthy mice without/with glucose stimulation (Figure). There was low imaging interference from organs adjacent to pancreas. 18F-TPA could detect the functional residue β-cells in diabetic mice. Biodistribution and immunostaining validated PET imaging results.
Conclusion: 18F-TPA PET imaging detected Zn2+ released from β-cells, reflecting insulin secretion capacity. It can be valuable for tracking in vivo β-cell function in future T1D treatment strategies.
J. Li: None. R. Yin: None. J. Rawson: None. F.R. Kandeel: Advisory Panel; Vertex Pharmaceuticals Incorporated.
the Oxnard Foundation (50214-2012049); WFP Mid-Term Innovative Award (10014-2011440)
