Mukesh K Pandey1, Aditya Bansal2, Hendrik P Engelbrecht2, John F Byrne3, Alan B Packard4, Timothy R DeGrado5. 1. Department of Radiology, Mayo Clinic Rochester MN 55905. Electronic address: pandey.mukesh@mayo.edu. 2. Department of Radiology, Mayo Clinic Rochester MN 55905. 3. Division of Nuclear Medicine, Brigham and Women's Hospital, Harvard Medical School Boston MA 02115. 4. Division of Nuclear Medicine and Molecular Imaging, Boston Children's Hospital, Harvard Medical School Boston MA 02115. 5. Department of Radiology, Mayo Clinic Rochester MN 55905. Electronic address: degrado.timothy@mayo.edu.
Abstract
OBJECTIVE: The objectives of the present work were to improve the cyclotron production yield of (89)Zr using a solution target, develop a practical synthesis of the hydroxamate resin used to process the target, and develop a biocompatible medium for (89)Zr elution from the hydroxamate resin. METHODS: A new solution target (BMLT-2) with enhanced heat dissipation capabilities was designed by using helium-cooled dual foils (0.2 mm Al and 25 μ Havar) and an enhanced water-cooled, elongated solution cavity in the target insert. Irradiations were performed with 14 MeV protons on a 2M solution of yttrium nitrate in 1.25 M nitric acid at 40-μA beam current for 2 h in a closed system. Zirconium-89 was separated from Y by use of a hydroxamate resin. A one-pot synthesis of hydroxamate resin was accomplished by activating the carboxylate groups on a carboxymethyl cation exchange resin using methyl chloroformate followed by reaction with hydroxylamine hydrochloride. After trapping of (89)Zr on hydroxamate resin and rinsing the resin with HCl and water to release Y, (89)Zr was eluted with 1.2 M K2HPO4/KH2PO4 buffer (pH3.5). ICP-MS was used to measure metal contaminants in the final (89)Zr solution. RESULTS: The BMLT-2 target produced 349±49 MBq (9.4±1.2 mCi) of (89)Zr at the end of irradiation with a specific activity of 1.18±0.79 GBq/μg. The hydroxamate resin prepared using the new synthesis method showed a trapping efficiency of 93% with a 75 mg resin bed and 96-97% with a 100-120 mg resin bed. The elution efficiency of (89)Zr with 1.2M K2HPO4/KH2PO4 solution was found to be 91.7±3.7%, compared to >95% for 1 M oxalic acid. Elution with phosphate buffer gave very small levels of metal contaminants: Al=0.40-0.86 μg (n=2), Fe=1.22±0.71 μg (n=3), Y=0.29 μg (n=1). CONCLUSIONS: The BMLT-2 target allowed doubling of the beam current for production of (89)Zr, resulting in a greater than 2-fold increase in production yield in comparison with a conventional liquid target. The new one-pot synthesis of hydroxamate resin provides a simpler synthesis method for the (89)Zr trapping resin. Finally, phosphate buffer elutes the (89)Zrfrom the hydroxamate resin in high efficiency while at the same time providing a more biocompatible medium for subsequent use of (89)Zr.
OBJECTIVE: The objectives of the present work were to improve the cyclotron production yield of (89)Zr using a solution target, develop a practical synthesis of the hydroxamate resin used to process the target, and develop a biocompatible medium for (89)Zr elution from the hydroxamate resin. METHODS: A new solution target (BMLT-2) with enhanced heat dissipation capabilities was designed by using helium-cooled dual foils (0.2 mm Al and 25 μ Havar) and an enhanced water-cooled, elongated solution cavity in the target insert. Irradiations were performed with 14 MeV protons on a 2M solution of yttrium nitrate in 1.25 M nitric acid at 40-μA beam current for 2 h in a closed system. Zirconium-89 was separated from Y by use of a hydroxamate resin. A one-pot synthesis of hydroxamate resin was accomplished by activating the carboxylate groups on a carboxymethyl cation exchange resin using methyl chloroformate followed by reaction with hydroxylamine hydrochloride. After trapping of (89)Zr on hydroxamate resin and rinsing the resin with HCl and water to release Y, (89)Zr was eluted with 1.2 M K2HPO4/KH2PO4 buffer (pH3.5). ICP-MS was used to measure metal contaminants in the final (89)Zr solution. RESULTS: The BMLT-2 target produced 349±49 MBq (9.4±1.2 mCi) of (89)Zr at the end of irradiation with a specific activity of 1.18±0.79 GBq/μg. The hydroxamate resin prepared using the new synthesis method showed a trapping efficiency of 93% with a 75 mg resin bed and 96-97% with a 100-120 mg resin bed. The elution efficiency of (89)Zr with 1.2M K2HPO4/KH2PO4 solution was found to be 91.7±3.7%, compared to >95% for 1 M oxalic acid. Elution with phosphate buffer gave very small levels of metal contaminants: Al=0.40-0.86 μg (n=2), Fe=1.22±0.71 μg (n=3), Y=0.29 μg (n=1). CONCLUSIONS: The BMLT-2 target allowed doubling of the beam current for production of (89)Zr, resulting in a greater than 2-fold increase in production yield in comparison with a conventional liquid target. The new one-pot synthesis of hydroxamate resin provides a simpler synthesis method for the (89)Zr trapping resin. Finally, phosphate buffer elutes the (89)Zrfrom the hydroxamate resin in high efficiency while at the same time providing a more biocompatible medium for subsequent use of (89)Zr.
Authors: Clara T Nicolas; Raymond D Hickey; Kari L Allen; Zeji Du; Rebekah M Guthman; Robert A Kaiser; Bruce Amiot; Aditya Bansal; Mukesh K Pandey; Lukkana Suksanpaisan; Timothy R DeGrado; Scott L Nyberg; Joseph B Lillegard Journal: Surgery Date: 2018-06-06 Impact factor: 3.982
Authors: Paul A Ellison; Hector F Valdovinos; Stephen A Graves; Todd E Barnhart; Robert J Nickles Journal: Appl Radiat Isot Date: 2016-10-13 Impact factor: 1.513
Authors: Mukesh K Pandey; Aditya Bansal; Jason R Ellinghuysen; Daniel J Vail; Heather M Berg; Timothy R DeGrado Journal: Am J Nucl Med Mol Imaging Date: 2022-02-15
Authors: Clara T Nicolas; Robert A Kaiser; Raymond D Hickey; Kari L Allen; Zeji Du; Caitlin J VanLith; Rebekah M Guthman; Bruce Amiot; Lukkana Suksanpaisan; Bing Han; Maria Giovanna Francipane; Amin Cheikhi; Huailei Jiang; Aditya Bansal; Mukesh K Pandey; Ishan Garg; Val Lowe; Aditya Bhagwate; Daniel O'Brien; Jean-Pierre A Kocher; Timothy R DeGrado; Scott L Nyberg; Eric Lagasse; Joseph B Lillegard Journal: Mol Ther Methods Clin Dev Date: 2020-07-10 Impact factor: 6.698