TH-EF-207A-02: Imaging Pancreatic β-Cell Function with 51/52Mn-PET

Purpose: To image β-cells noninvasively using radio-manganese PET and to develop efficient small cyclotron production of ⁵¹Mn (t1/2=46m, β⁺=97%) and ⁵²Mn (t1/2=5.6d, β⁺=29%). Methods: ⁵¹Mn and ⁵²Mn were produced by 16 MeV proton irradiation (GE PETtrace) of electrodeposited ⁵⁴Fe on silver and Cr metal pressed into a silver disc, respectively. ⁵¹Mn was radiochemically isolated from target material by anion exchange chromatography and ⁵²Mn was isolated by ethanolic anion exchange trap-and-release. A final injectable product of ⁵¹Mn²⁺ or ⁵²Mn²⁺ was obtained in 0.01M pH 6.0 NaOAc. To assess pancreatic uptake, fasted ICR mice were administered and intravenous bolus or infusion of ⁵²Mn²⁺. Additionally, to demonstrate the correlation between β-cell function and ⁵²Mn²⁺ pancreatic uptake, prior to tracer administration groups of ICR mice were administered glibenclamide (5mg/kg) and diazoxide (20 mg/kg) as an insulin release stimulator and blocker, respectively. To validate PET ROI quantification, ex vivo biodistribtution studies were conducted on each subject after the final imaging time-point. Results: Dynamic PET data using a left atrium ROI revealed that ⁵²Mn²⁺ cleared from the blood with a 10 second half-life. Significant uptake was seen in the pancreas (approximately 20% ID/g, SUVmean= 5.5), liver, kidneys, intestine, heart, and thyroid. Pancreatic uptake was found to be highly sensitive to volatile anesthesia administration (p=0.0002), insulin release stimulation by glibenclamide (p=0.017), and by insulin release inhibition by diazoxide (p=0.046). Excellent agreement was found between in vivo PET ROI quantification and ex vivo biodistribution measurements. Conclusion: This work demonstrates the feasibility of using radiomanganese-PET for measuring functional β-cell mass in vivo. The decay characteristics and dosimetric properties of ⁵¹Mn are well suited for clinical PET, which will allow for rapid translation and application.