Novel 51Mn production methods for calcium channel transport based applications

380 Objectives The need for a short-lived and low-dose alternative to 52gMn (t1/2=5.59 days, β+=29.6%), which has several high energy gamma rays, has arisen for calcium channel transport applications such as measuring pancreatic functional β-cell mass. 51Mn (t1/2=46 min, β+=97.1%) presents itself as an excellent candidate for this role, as it may be produced in GBq quantities on low-energy cyclotrons ( Methods 54Fe targets were prepared by electrodeposition on a silver disc as previously described (Valdovinos et al., J. Nuc. Med., 2015). Briefly, isotopically enriched 54Fe metal (Isoflex Inc.) was dissolved in 6M HCl, and then taken to dryness at 130°C under N2 flow. The iron chloride was reconstituted in 15 mL saturated ammonium oxalate solution. To this 100mg of L-ascorbic acid and 100 µl of 30% H2O2 was added, and the pH was adjusted to pH 3.0 using 6M HCl or NaOH. Plating was performed using a platinum wire anode approximately 1 cm above the silver disc substrate (0.5 mm thick, 0.75” diameter). Plating voltage was set to 7.0V across the cell which corresponded to an initial current density of approximately 0.17 A/cm2. Plating was allowed to take place for 24-48 hours, until the electrolyte solution was colorless. Targets of thickness 45-65 mg/cm2 were irradiated by 30 µA of 16 MeV protons (GE PETtrace) for one hour, before being dissolved in 2mL 11M HCl at 80°C for 20 min. To this solution 1.8mL H2O and 200 µl 30% H2O2 was added before being loaded onto a 15 mL AG-1x8 column (1.5cm diameter) equilibrated with 5M HCl. Using 5M HCl as mobile phase, the first 5 mL of eluant was discarded, and the following 10 mL of eluant containing the 51Mn activity was collected and taken to dryness under reduced pressure. The activity was reconstituted in 0.5-1.0mL of 0.1M HCl or pH 6 0.01M NaOAc. The column was rinsed by an additional 30 mL 5M HCl, and the 54Fe target material was recovered from the column in 30-50 mL of 0.1M HCl. Results Targets withstood the 30 µA beam current with no visible damage. The average end of bombardment (EoB) 51Mn yield was found to be 1.91 GBq (n=3) for target thicknesses of 64.4, 58.1 and 46.2 mg/cm2. Decay corrected radiochemical yield was found to be 67.3 ± 12.6% (n=3). With an average chemistry duration under 90 minutes, an overall end of separation yield of 18.4 ± 4.0% (n=3) was obtained. 54Fe recovery was found to be highly efficient with an average plated recovery of 94.3 ± 4.2% (n=3). Microwave plasma atomic emission spectrometry (MP-AES, Agilent Inc.) trace metal analysis was performed to measure the Fe content of the 51Mn product. An average Fe load of 3.2 ± 4.9 µg (n=3) was measured corresponding to an average separation factor of (9.3 ± 14.2) x103. Conclusions A novel, rapid and efficient 51Mn production method for low-energy cyclotrons from isotopically enriched 54Fe targets has been developed. The superior decay characteristics of 51Mn make it an excellent candidate for clinical translation. This work will allow for immediate 51Mn application in pre-clinical calcium channel transport studies, including the non-invasive quantification of functional β-cell mass.