2014 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 first year of the current project several task were successfully accomplished, but some of them are still ongoing and might need to be reconsidered concerning the original propose. In this regard, and following the proposed research plan, the evaluation of two new N-acetyl-D-glucosamine (NAG) derivatives was performed. The 2-methanesulfonyl and 2-(p-toluenesulfonyl) derivatives of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-acetamido-D-glucopyranose were synthesized and structures were in accordance with analytical data. Next, the efficiency of [18F]fluoride incorporation into them was evaluated. [18F]fluorination under microwaves irradiation conditions or conventional heating were compared with previous 2-bromoacetamido derivative. New derivatives were able to incorporate [18F]F－ under microwaves irradiation or conventional heating conditions. Microwave significantly enhanced the [18F]F－ incorporation to >85% (up to 35% improvement), while reducing times to 5 min (~10-fold reduction), compared with conventional heating. Also radiosynthesis of N-fluoroacetyl-D-glucosamine ([18F]FAG) using 2-(p-toluenesulfonyl) derivatives was accomplished by a semiautomatic system developed in our center. In addition, an HPLC method was developed for quality control of final [18F]FAG. Consequently non-radioactive FAG, as standard, and other analogues were synthesized in our laboratory. The HPLC method is currently applied for purification and analysis of [18F]FAG after radiosynthesis in our laboratory.
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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 two task could not be performed on schedule. The in-vitro evaluation of UDP-[18F]FAG from originally radiosynthesized [18F]FAG, as well as, the confirmation of cellular levels of UDP-[18F]FAG have not been accomplished. The main reason for that breach of plan have been the impossibility to improve the final radiochemical yield and specific activity. The use of 2-(p-toluenesulfonyl) derivatives as a precursor improved the HPLC purification procedure since retention time of free unlabelled precursor is 7 min difference with [18F]FAG while using 2-bromoacetamido is only 2. Nevertheless, injection volume of sample and remained radioactivity inside HPLC column still affect the final recovery.
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| Strategy for Future Research Activity |
Currently we are working to reduce the volume of sample before injection into HPLC. This must increase the resolution between peaks and therefore increase recovery and specific activity. To overcome above mention troubles and considering that a future pre-clinical or animal evaluation of final [18F]FAG using 2-(p-toluenesulfonyl) derivatives as a precursor still require time. We propose to start, in parallel the synthesis of UDP-NAG derivatives as precursors for UDP-[18F]FAG radiosynthesis. This include the synthesis of non-radioactive UDP-FAG, as standard, and any other possible interference.
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| Causes of Carryover |
As was mention before, there was a breach of research plan where we were not able to perform the in-vitro studies on schedule. This amount of money was destined to the acquisition of reagents, disposable laboratory supplies and cell culture media to perform those studies.
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| Expenditure Plan for Carryover Budget |
Currently we will continue working to improve the final radiochemical yield and specific activity of [18F]FAG. Therefore, the money will still be use for its original purpose of acquisition of reagents, disposable laboratory supplies and cell culture media to perform the in-vitro studies.
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