Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer
Abstract Background The demand for 68Ga-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic application...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-12-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41181-023-00229-9 |
| _version_ | 1827581321435676672 |
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| author | Hemantha Mallapura Olga Ovdiichuk Emma Jussing Tran A. Thuy Camille Piatkowski Laurent Tanguy Charlotte Collet-Defossez Bengt Långström Christer Halldin Sangram Nag |
| author_facet | Hemantha Mallapura Olga Ovdiichuk Emma Jussing Tran A. Thuy Camille Piatkowski Laurent Tanguy Charlotte Collet-Defossez Bengt Långström Christer Halldin Sangram Nag |
| author_sort | Hemantha Mallapura |
| collection | DOAJ |
| description | Abstract Background The demand for 68Ga-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic applications, fueling interest in exploring them for clinical use. Among these probes, 68Ga-labeled FAPI-46 and DOTA-TOC have emerged as key players due to their ability to diagnose a broad spectrum of cancers ([68Ga]Ga-FAPI-46) in late-phase studies, whereas [68Ga]Ga-DOTA-TOC is clinically approved for neuroendocrine tumors. To facilitate their production, we leveraged a microfluidic cassette-based iMiDEV radiosynthesizer, enabling the synthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC based on a dose-on-demand (DOD) approach. Results Different mixing techniques were explored to influence radiochemical yield. We achieved decay-corrected yield of 44 ± 5% for [68Ga]Ga-FAPI-46 and 46 ± 7% for [68Ga]Ga-DOTA-TOC in approximately 30 min. The radiochemical purities (HPLC) of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC were 98.2 ± 0.2% and 98.4 ± 0.9%, respectively. All the quality control results complied with European Pharmacopoeia quality standards. We optimized various parameters, including 68Ga trapping and elution, cassette batches, passive mixing in the reactor, and solid-phase extraction (SPE) purification and formulation. The developed synthesis method reduced the amount of precursor and other chemicals required for synthesis compared to conventional radiosynthesizers. Conclusions The microfluidic-based approach enabled the implementation of radiosynthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC on the iMiDEV™ microfluidic module, paving the way for their use in preclinical and clinical applications. The microfluidic synthesis approach utilized 2–3 times less precursor than cassette-based conventional synthesis. The synthesis method was also successfully validated in a similar microfluidic iMiDEV module at a different research center for the synthesis of [68Ga]Ga-FAPI-46 with limited runs. Our study demonstrated the potential of microfluidic methods for efficient and reliable radiometal-based radiopharmaceutical synthesis, contributing valuable insights for future advancements in this field and paving the way for routine clinical applications in the near future. |
| first_indexed | 2024-03-08T22:34:43Z |
| format | Article |
| id | doaj.art-db04fb5707a847efbc286e4b85fa40ce |
| institution | Directory Open Access Journal |
| issn | 2365-421X |
| language | English |
| last_indexed | 2024-03-08T22:34:43Z |
| publishDate | 2023-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj.art-db04fb5707a847efbc286e4b85fa40ce2023-12-17T12:34:05ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2023-12-018112110.1186/s41181-023-00229-9Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizerHemantha Mallapura0Olga Ovdiichuk1Emma Jussing2Tran A. Thuy3Camille Piatkowski4Laurent Tanguy5Charlotte Collet-Defossez6Bengt Långström7Christer Halldin8Sangram Nag9Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County CouncilNancyclotep, Molecular Imaging PlatformDepartment of Oncology and Pathology, Karolinska InstitutetDepartment of Oncology and Pathology, Karolinska InstitutetPMB-AlcenPMB-AlcenNancyclotep, Molecular Imaging PlatformDepartment of Chemistry, Uppsala UniversityDepartment of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County CouncilDepartment of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County CouncilAbstract Background The demand for 68Ga-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic applications, fueling interest in exploring them for clinical use. Among these probes, 68Ga-labeled FAPI-46 and DOTA-TOC have emerged as key players due to their ability to diagnose a broad spectrum of cancers ([68Ga]Ga-FAPI-46) in late-phase studies, whereas [68Ga]Ga-DOTA-TOC is clinically approved for neuroendocrine tumors. To facilitate their production, we leveraged a microfluidic cassette-based iMiDEV radiosynthesizer, enabling the synthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC based on a dose-on-demand (DOD) approach. Results Different mixing techniques were explored to influence radiochemical yield. We achieved decay-corrected yield of 44 ± 5% for [68Ga]Ga-FAPI-46 and 46 ± 7% for [68Ga]Ga-DOTA-TOC in approximately 30 min. The radiochemical purities (HPLC) of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC were 98.2 ± 0.2% and 98.4 ± 0.9%, respectively. All the quality control results complied with European Pharmacopoeia quality standards. We optimized various parameters, including 68Ga trapping and elution, cassette batches, passive mixing in the reactor, and solid-phase extraction (SPE) purification and formulation. The developed synthesis method reduced the amount of precursor and other chemicals required for synthesis compared to conventional radiosynthesizers. Conclusions The microfluidic-based approach enabled the implementation of radiosynthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC on the iMiDEV™ microfluidic module, paving the way for their use in preclinical and clinical applications. The microfluidic synthesis approach utilized 2–3 times less precursor than cassette-based conventional synthesis. The synthesis method was also successfully validated in a similar microfluidic iMiDEV module at a different research center for the synthesis of [68Ga]Ga-FAPI-46 with limited runs. Our study demonstrated the potential of microfluidic methods for efficient and reliable radiometal-based radiopharmaceutical synthesis, contributing valuable insights for future advancements in this field and paving the way for routine clinical applications in the near future.https://doi.org/10.1186/s41181-023-00229-9Positron emission tomography (PET)RadiopharmaceuticalsMicrofluidicsiMiDEV[68Ga]Ga-FAPI-46[68Ga]Ga-DOTA-TOC |
| spellingShingle | Hemantha Mallapura Olga Ovdiichuk Emma Jussing Tran A. Thuy Camille Piatkowski Laurent Tanguy Charlotte Collet-Defossez Bengt Långström Christer Halldin Sangram Nag Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer EJNMMI Radiopharmacy and Chemistry Positron emission tomography (PET) Radiopharmaceuticals Microfluidics iMiDEV [68Ga]Ga-FAPI-46 [68Ga]Ga-DOTA-TOC |
| title | Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer |
| title_full | Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer |
| title_fullStr | Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer |
| title_full_unstemmed | Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer |
| title_short | Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer |
| title_sort | microfluidic based production of 68ga ga fapi 46 and 68ga ga dota toc using the cassette based imidev™ microfluidic radiosynthesizer |
| topic | Positron emission tomography (PET) Radiopharmaceuticals Microfluidics iMiDEV [68Ga]Ga-FAPI-46 [68Ga]Ga-DOTA-TOC |
| url | https://doi.org/10.1186/s41181-023-00229-9 |
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