2015 Fiscal Year Research-status Report
Development of F-18 radiopharmaceutical for PET imaging of infections
| Project/Area Number |
26461786
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| Research Institution | University of Fukui |
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Principal Investigator |
Martinez Miguel 福井大学, 高エネルギー医学研究センター, 特命助教 (00631491)
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| Co-Investigator(Kenkyū-buntansha) |
清野 泰 福井大学, 高エネルギー医学研究センター, 教授 (50305603)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | PET / infection / inflammation / Bacterial imaging agent / Glucosamine derivatives |
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| Outline of Annual Research Achievements |
During the past year we concluded the development of a high-performance liquid chromatography (HPLC) method for quality control of final [18F]FAG. HPLC method was validated for specificity, linearity, accuracy, precision, limit of detection, and limit of quantitation using FAG and acetylglucosamine (NAG) as standard. The new method exhibited better sensitivity and detection than our previous reported HPLC method. Furthermore, we worked to increase the final specific activity through modifications introduced to the original purification protocol. Two purification protocols were evaluated. Purification using only amino-bonded silica phase column gave specific activity values of 1.4±0.3×10-3 and 2.1±0.2×10-3 GBq/μmol for bromo and tosylate precursors respectively. Whereas, when amino column was followed by a C18 column the specific activity values obtained were 7.8±4.4×10-2 and 8.0±1.9×10-2 GBq/μmol for bromo and tosylate precursors respectively. Further analysis by ESI-MS found that purification using amino column was affected by a common by-product contaminant with similar elution time that final [18F]FAG. The addition of a C18 bonded silica phase column help to separate this by-product and can explain the observed increment by ten-fold in the final specific activity.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
According to the original proposed research plan in-vitro evaluation of UDP-[18F]FAG from originally synthesized [18F]FAG, assessing cellular levels of UDP-[18F]FAG and animal experiments were not accomplished on time mainly due to low specific activity (SA) of final [18F]FAG. Currently, specific activity was improved by 10-fold, nevertheless, radiochemical yields remain low which difficult the correct performance of above mention experiments.
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| Strategy for Future Research Activity |
Recently, after some modifications to the purification protocol specific activity was improved, but still the radiochemical yield remain low which will conspire again future animal experiments or clinical trials. Therefore, we are considering to not perform the in-vitro evaluation and give continuity to the project with the synthesis and evaluation of new UDP-N-acetylglucosamine derivatives.
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| Causes of Carryover |
In order to advance in the final stage of the project and accomplish the synthesis and evaluation of UDP-N-acetylglucosamine derivatives, according to the original research plan proposal.
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| Expenditure Plan for Carryover Budget |
The requested amount of money will be used according to the research proposal to acquire the necessary reagent and labware supplies for the synthesis of UDP-N-acetylglucosamine derivatives, as well as, the travel expenses to attend the Annual Meeting of the European association of Nuclear medicine (EANM'16) in Barcelona, Spain.
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