A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben
Abstract Background Current automated radiosynthesizers are generally optimized for producing large batches of PET tracers. Preclinical imaging studies, however, often require only a small portion of a regular batch, which cannot be economically produced on a conventional synthesizer. Alternative ap...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-12-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-020-00113-w |
| _version_ | 1818854362557972480 |
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| author | Ksenia Lisova Jia Wang Philip H. Chao R. Michael van Dam |
| author_facet | Ksenia Lisova Jia Wang Philip H. Chao R. Michael van Dam |
| author_sort | Ksenia Lisova |
| collection | DOAJ |
| description | Abstract Background Current automated radiosynthesizers are generally optimized for producing large batches of PET tracers. Preclinical imaging studies, however, often require only a small portion of a regular batch, which cannot be economically produced on a conventional synthesizer. Alternative approaches are desired to produce small to moderate batches to reduce cost and the amount of reagents and radioisotope needed to produce PET tracers with high molar activity. In this work we describe the first reported microvolume method for production of [18F]Florbetaben for use in imaging of Alzheimer’s disease. Procedures The microscale synthesis of [18F]Florbetaben was adapted from conventional-scale synthesis methods. Aqueous [18F]fluoride was azeotropically dried with K2CO3/K222 (275/383 nmol) complex prior to radiofluorination of the Boc-protected precursor (80 nmol) in 10 μL DMSO at 130 °C for 5 min. The resulting intermediate was deprotected with HCl at 90 °C for 3 min and recovered from the chip in aqueous acetonitrile solution. The crude product was purified via analytical scale HPLC and the collected fraction reformulated via solid-phase extraction using a miniature C18 cartridge. Results Starting with 270 ± 100 MBq (n = 3) of [18F]Fluoride, the method affords formulated product with 49 ± 3% (decay-corrected) yield,> 98% radiochemical purity and a molar activity of 338 ± 55 GBq/μmol. The miniature C18 cartridge enables efficient elution with only 150 μL of ethanol which is diluted to a final volume of 1.0 mL, thus providing a sufficient concentration for in vivo imaging. The whole procedure can be completed in 55 min. Conclusions This work describes an efficient and reliable procedure to produce [18F]Florbetaben in quantities sufficient for large-scale preclinical applications. This method provides very high yields and molar activities compared to reported literature methods. This method can be applied to higher starting activities with special consideration given to automation and radiolysis prevention. |
| first_indexed | 2024-12-19T07:51:30Z |
| format | Article |
| id | doaj.art-41d87cda5a4440de8c10cacbf7ebced2 |
| institution | Directory Open Access Journal |
| issn | 2365-421X |
| language | English |
| last_indexed | 2024-12-19T07:51:30Z |
| publishDate | 2020-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj.art-41d87cda5a4440de8c10cacbf7ebced22022-12-21T20:30:09ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2020-12-015111610.1186/s41181-020-00113-wA simple and efficient automated microvolume radiosynthesis of [18F]FlorbetabenKsenia Lisova0Jia Wang1Philip H. Chao2R. Michael van Dam3Physics & Biology in Medicine Interdepartmental Graduate Program, University of California Los AngelesCrump Institute for Molecular Imaging, University of California Los AngelesCrump Institute for Molecular Imaging, University of California Los AngelesPhysics & Biology in Medicine Interdepartmental Graduate Program, University of California Los AngelesAbstract Background Current automated radiosynthesizers are generally optimized for producing large batches of PET tracers. Preclinical imaging studies, however, often require only a small portion of a regular batch, which cannot be economically produced on a conventional synthesizer. Alternative approaches are desired to produce small to moderate batches to reduce cost and the amount of reagents and radioisotope needed to produce PET tracers with high molar activity. In this work we describe the first reported microvolume method for production of [18F]Florbetaben for use in imaging of Alzheimer’s disease. Procedures The microscale synthesis of [18F]Florbetaben was adapted from conventional-scale synthesis methods. Aqueous [18F]fluoride was azeotropically dried with K2CO3/K222 (275/383 nmol) complex prior to radiofluorination of the Boc-protected precursor (80 nmol) in 10 μL DMSO at 130 °C for 5 min. The resulting intermediate was deprotected with HCl at 90 °C for 3 min and recovered from the chip in aqueous acetonitrile solution. The crude product was purified via analytical scale HPLC and the collected fraction reformulated via solid-phase extraction using a miniature C18 cartridge. Results Starting with 270 ± 100 MBq (n = 3) of [18F]Fluoride, the method affords formulated product with 49 ± 3% (decay-corrected) yield,> 98% radiochemical purity and a molar activity of 338 ± 55 GBq/μmol. The miniature C18 cartridge enables efficient elution with only 150 μL of ethanol which is diluted to a final volume of 1.0 mL, thus providing a sufficient concentration for in vivo imaging. The whole procedure can be completed in 55 min. Conclusions This work describes an efficient and reliable procedure to produce [18F]Florbetaben in quantities sufficient for large-scale preclinical applications. This method provides very high yields and molar activities compared to reported literature methods. This method can be applied to higher starting activities with special consideration given to automation and radiolysis prevention.https://doi.org/10.1186/s41181-020-00113-wMicrofluidicsRadiochemistryBeta-amyloid imagingFlorbetabenMolar activityDroplet synthesis |
| spellingShingle | Ksenia Lisova Jia Wang Philip H. Chao R. Michael van Dam A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben EJNMMI Radiopharmacy and Chemistry Microfluidics Radiochemistry Beta-amyloid imaging Florbetaben Molar activity Droplet synthesis |
| title | A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben |
| title_full | A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben |
| title_fullStr | A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben |
| title_full_unstemmed | A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben |
| title_short | A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben |
| title_sort | simple and efficient automated microvolume radiosynthesis of 18f florbetaben |
| topic | Microfluidics Radiochemistry Beta-amyloid imaging Florbetaben Molar activity Droplet synthesis |
| url | https://doi.org/10.1186/s41181-020-00113-w |
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