Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]Choline
Microfluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L...
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MDPI AG
2024-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/17/2/250 |
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| author | Hemantha Mallapura Laurent Tanguy Samin Mahfuz Lovisa Bylund Bengt Långström Christer Halldin Sangram Nag |
| author_facet | Hemantha Mallapura Laurent Tanguy Samin Mahfuz Lovisa Bylund Bengt Långström Christer Halldin Sangram Nag |
| author_sort | Hemantha Mallapura |
| collection | DOAJ |
| description | Microfluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L-[<sup>11</sup>C]methionine and [<sup>11</sup>C]choline, was performed, using a microfluidic cassette and an iMiDEV<sup>TM</sup> module by employing a dose-on-demand approach for the synthesis process. We focused on optimizing the precursor amounts and radiosynthesis on the microfluidic cassette. L-[<sup>11</sup>C]methionine and [<sup>11</sup>C]choline were synthesized using a microreactor filled with a suitable resin for the radiochemical reaction. Trapping of the [<sup>11</sup>C]methyl iodide, its reaction, and solid-phase extraction purification were performed on a microreactor, achieving radiochemical yields of >80% for L-[<sup>11</sup>C]methionine and >60% for [<sup>11</sup>C]choline (<i>n</i> = 3). The total synthesis time for both the radiotracers was approximately 20 min. All quality control tests complied with the European Pharmacopeia standards. The dose-on-demand model allows for real-time adaptation to patient schedules, making it suitable for preclinical and clinical settings. Precursor optimization enhanced the cost efficiency without compromising the yield. The importance of dose-on-demand synthesis and optimized precursor utilization to produce L-[<sup>11</sup>C]methionine and [<sup>11</sup>C]choline was emphasized in this study. The results demonstrated the feasibility of dose-on-demand adaptations for clinical applications with reduced precursor quantities and high radiochemical yields. |
| first_indexed | 2024-03-07T22:17:38Z |
| format | Article |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-07T22:17:38Z |
| publishDate | 2024-02-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-259044743f334c2292295fae66132a7a2024-02-23T15:30:51ZengMDPI AGPharmaceuticals1424-82472024-02-0117225010.3390/ph17020250Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]CholineHemantha Mallapura0Laurent Tanguy1Samin Mahfuz2Lovisa Bylund3Bengt Långström4Christer Halldin5Sangram Nag6Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, SE-17176 Stockholm, SwedenBusiness Unit Nuclear Medicine, PMB-Alcen, Route des Michels CD56, F-13790 Peynier, FranceDepartment of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, SE-17176 Stockholm, SwedenDepartment of Radiopharmacy, Karolinska University Hospital, SE-17176 Stockholm, SwedenDepartment of Medicinal Chemistry, Uppsala University, SE-75123 Uppsala, SwedenDepartment of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, SE-17176 Stockholm, SwedenDepartment of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, SE-17176 Stockholm, SwedenMicrofluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L-[<sup>11</sup>C]methionine and [<sup>11</sup>C]choline, was performed, using a microfluidic cassette and an iMiDEV<sup>TM</sup> module by employing a dose-on-demand approach for the synthesis process. We focused on optimizing the precursor amounts and radiosynthesis on the microfluidic cassette. L-[<sup>11</sup>C]methionine and [<sup>11</sup>C]choline were synthesized using a microreactor filled with a suitable resin for the radiochemical reaction. Trapping of the [<sup>11</sup>C]methyl iodide, its reaction, and solid-phase extraction purification were performed on a microreactor, achieving radiochemical yields of >80% for L-[<sup>11</sup>C]methionine and >60% for [<sup>11</sup>C]choline (<i>n</i> = 3). The total synthesis time for both the radiotracers was approximately 20 min. All quality control tests complied with the European Pharmacopeia standards. The dose-on-demand model allows for real-time adaptation to patient schedules, making it suitable for preclinical and clinical settings. Precursor optimization enhanced the cost efficiency without compromising the yield. The importance of dose-on-demand synthesis and optimized precursor utilization to produce L-[<sup>11</sup>C]methionine and [<sup>11</sup>C]choline was emphasized in this study. The results demonstrated the feasibility of dose-on-demand adaptations for clinical applications with reduced precursor quantities and high radiochemical yields.https://www.mdpi.com/1424-8247/17/2/250positron emission tomographyiMiDEVmicrofluidic cassettebatch-type microfluidicsradiosynthesizerradiosynthesis |
| spellingShingle | Hemantha Mallapura Laurent Tanguy Samin Mahfuz Lovisa Bylund Bengt Långström Christer Halldin Sangram Nag Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]Choline Pharmaceuticals positron emission tomography iMiDEV microfluidic cassette batch-type microfluidics radiosynthesizer radiosynthesis |
| title | Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]Choline |
| title_full | Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]Choline |
| title_fullStr | Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]Choline |
| title_full_unstemmed | Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]Choline |
| title_short | Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[<sup>11</sup>C]Methionine and [<sup>11</sup>C]Choline |
| title_sort | advancements in microfluidic cassette based imidev™ technology for production of l sup 11 sup c methionine and sup 11 sup c choline |
| topic | positron emission tomography iMiDEV microfluidic cassette batch-type microfluidics radiosynthesizer radiosynthesis |
| url | https://www.mdpi.com/1424-8247/17/2/250 |
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