期刊
RSC ADVANCES
卷 9, 期 64, 页码 37214-37221出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9ra07723e
关键词
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资金
- Cancer Research UK Career Establishment Award [C63178/A24959]
- Swiss National Science Foundation through an Advanced Postdoc Mobility Fellowship [P300P2-177855_1]
- London Metallomics Facility - Wellcome Trust Multi-user Equipment Grant [202902/Z/16/Z]
- Centre for Medical Engineering - Wellcome Trust [WT088641/Z/09/Z]
- Centre for Medical Engineering - Engineering and Physical Sciences Research Council [WT088641/Z/09/Z]
- King's College London
- University College London Comprehensive Cancer Imaging Centre - Cancer Research UK
- EPSRC
- Medical Research Council
- Department of Health (England)
- National Institute for Health Research Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London (KCL)
- EPSRC [EP/S032789/1] Funding Source: UKRI
- Swiss National Science Foundation (SNF) [P300P2_177855] Funding Source: Swiss National Science Foundation (SNF)
GMP-grade Ge-68/Ga-68 generators provide access to positron-emitting Ga-68, enabling preparation of Positron Emission Tomography (PET) tracers and PET imaging at sites that do not have access to cyclotron-produced radionuclides. Radiotracers based on tris(3-hydroxy-1,6-dimethylpyridin-4-one) (THP) chelators enable simple one-step preparations of Ga-68 PET radiopharmaceuticals from pre-fabricated kits without pre-processing of generator eluate or post-purification. However, trace metal impurities eluted along with Ga-68 could compete for THP and reduce radiochemical yields (RCY). We have quantified trace metal impurities in Ga-68 eluate from an Eckert & Ziegler (E&Z) generator using ICP-MS. The metals Al, Fe, Ga-nat, Pb, Ti and Zn-nat were present in generator eluate in significantly higher concentrations than in the starting eluent solution. Concentrations of Fe and Ga-nat in eluate were in the range of 0.01-0.1 mu M, Al, Zn and Pb in the range of 0.1-1 mu M, and Ti in the range of 0.9-1.5 mu M. To assess the ability of THP to chelate Ga-68 in the presence of such metal ions, radiolabelling reactions were undertaken in which selected metal ions were added to make them equimolar with THP, or higher. Al3+, Fe3+, Ga-nat(3+) and Ti4+ reduced RCY at concentrations equimolar with THP and higher, but at lower concentrations they did not affect RCY. Pb2+, Zn2+, Ni2+ and Cr3+ had no effect on RCY (even under conditions in which each metal ion was present in 100-fold molar excess over THP). The multi-sample ICP-MS analysis reported here is (to date) the most comprehensive and robust quantification of metal impurities in the widely used E&Z Ga-68 generator. Ga-68 from an E&Z generator enables near-quantitative radiolabelling of THP at chelator concentrations as low as 5 mu M (lower than other common gallium chelators) without pre-processing. The combination of Al3+, Fe3+, Ga-nat(3+) and Ti4+ in unprocessed Ga-68 eluate is likely to decrease RCY of Ga-68 radiolabelling if a lower amount of THP chelator is used, and future kit design should take this into account. To increase specific activities by using even lower THP concentrations, purification of Ga-68 from trace metal ions will likely be required.
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