Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules
Abstract Background Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[18F]fluoronicotinic acid ([18F]FNA) have been prepared and successfully employed for 18F-labeling of diverse biomolecules, including peptides. The utility...
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SpringerOpen
2025-07-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-025-00368-1 |
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| author | Pyry Dillemuth Abiodun Ayo Xiaoqing Zhuang Petter Lövdahl Heidi Liljenbäck Salli Kärnä Tatsiana Auchynnikava Jonne Kunnas Jesse Ponkamo Maxwell W. G. Miner Johan Rajander Jessica M. Rosenholm Anne Roivainen Anu J. Airaksinen Pirjo Laakkonen Xiang-Guo Li |
| author_facet | Pyry Dillemuth Abiodun Ayo Xiaoqing Zhuang Petter Lövdahl Heidi Liljenbäck Salli Kärnä Tatsiana Auchynnikava Jonne Kunnas Jesse Ponkamo Maxwell W. G. Miner Johan Rajander Jessica M. Rosenholm Anne Roivainen Anu J. Airaksinen Pirjo Laakkonen Xiang-Guo Li |
| author_sort | Pyry Dillemuth |
| collection | DOAJ |
| description | Abstract Background Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[18F]fluoronicotinic acid ([18F]FNA) have been prepared and successfully employed for 18F-labeling of diverse biomolecules, including peptides. The utility of [18F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors. This study aims to evaluate a [18F]FNA-conjugated nonapeptide, [18F]FNA-N-CooP, for positron emission tomography imaging of intracranial BT12 glioblastoma xenografts in a mouse model. Additionally, this study highlights the importance of including control experiments with prosthetic compound alone when it constitutes a major radiometabolite. Results [18F]FNA-N-CooP successfully delineated intracranial glioblastoma xenografts yielding a standardized uptake value of 0.21 ± 0.03 (n = 4) and a tumor-to-brain ratio of 1.84 ± 0.29. Ex vivo autoradiography of tumor tissue showed a partial co-localization between radioactivity uptake and the target fatty acid binding protein 3 expression. However, in vivo instability of [18F]FNA-N-CooP was observed, with [18F]FNA identified as a major radiometabolite. Notably, control studies using [18F]FNA alone also visualized tumors, producing a standardized uptake value of 0.90 ± 0.10 (n = 4) and a tumor-to-brain ratio of 1.51 ± 0.08. Conclusions Both [18F]FNA-N-CooP and [18F]FNA enabled PET visualization of human glioblastoma in the mouse model. However, the prominent presence of [18F]FNA as radiometabolite complicates the interpretation of [18F]FNA-N-CooP PET data, suggesting that the observed radioactivity uptake may primarily originate from [18F]FNA and other radiometabolites. Enhancing peptide stability is essential for improving imaging specificity. This study underscores the critical need to assess the imaging contributions of prosthetic groups when they function as significant radiometabolites. |
| format | Article |
| id | doaj-art-75d7aeb5aa8b4904bafdb15d625b7b66 |
| institution | Kabale University |
| issn | 2365-421X |
| language | English |
| publishDate | 2025-07-01 |
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| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-75d7aeb5aa8b4904bafdb15d625b7b662025-08-20T03:42:04ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2025-07-0110111510.1186/s41181-025-00368-1Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomoleculesPyry Dillemuth0Abiodun Ayo1Xiaoqing Zhuang2Petter Lövdahl3Heidi Liljenbäck4Salli Kärnä5Tatsiana Auchynnikava6Jonne Kunnas7Jesse Ponkamo8Maxwell W. G. Miner9Johan Rajander10Jessica M. Rosenholm11Anne Roivainen12Anu J. Airaksinen13Pirjo Laakkonen14Xiang-Guo Li15Turku PET Centre, University of TurkuTranslational Cancer Medicine Research Program, Faculty of Medicine, University of HelsinkiTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuPharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi UniversityTurku PET Centre, University of TurkuTurku PET Centre, University of TurkuTranslational Cancer Medicine Research Program, Faculty of Medicine, University of HelsinkiTurku PET Centre, University of TurkuAbstract Background Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[18F]fluoronicotinic acid ([18F]FNA) have been prepared and successfully employed for 18F-labeling of diverse biomolecules, including peptides. The utility of [18F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors. This study aims to evaluate a [18F]FNA-conjugated nonapeptide, [18F]FNA-N-CooP, for positron emission tomography imaging of intracranial BT12 glioblastoma xenografts in a mouse model. Additionally, this study highlights the importance of including control experiments with prosthetic compound alone when it constitutes a major radiometabolite. Results [18F]FNA-N-CooP successfully delineated intracranial glioblastoma xenografts yielding a standardized uptake value of 0.21 ± 0.03 (n = 4) and a tumor-to-brain ratio of 1.84 ± 0.29. Ex vivo autoradiography of tumor tissue showed a partial co-localization between radioactivity uptake and the target fatty acid binding protein 3 expression. However, in vivo instability of [18F]FNA-N-CooP was observed, with [18F]FNA identified as a major radiometabolite. Notably, control studies using [18F]FNA alone also visualized tumors, producing a standardized uptake value of 0.90 ± 0.10 (n = 4) and a tumor-to-brain ratio of 1.51 ± 0.08. Conclusions Both [18F]FNA-N-CooP and [18F]FNA enabled PET visualization of human glioblastoma in the mouse model. However, the prominent presence of [18F]FNA as radiometabolite complicates the interpretation of [18F]FNA-N-CooP PET data, suggesting that the observed radioactivity uptake may primarily originate from [18F]FNA and other radiometabolites. Enhancing peptide stability is essential for improving imaging specificity. This study underscores the critical need to assess the imaging contributions of prosthetic groups when they function as significant radiometabolites.https://doi.org/10.1186/s41181-025-00368-1Fluorine-186-[18F]fluoronicotinic acidPeptide radiolabelingPETProsthetic group |
| spellingShingle | Pyry Dillemuth Abiodun Ayo Xiaoqing Zhuang Petter Lövdahl Heidi Liljenbäck Salli Kärnä Tatsiana Auchynnikava Jonne Kunnas Jesse Ponkamo Maxwell W. G. Miner Johan Rajander Jessica M. Rosenholm Anne Roivainen Anu J. Airaksinen Pirjo Laakkonen Xiang-Guo Li Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules EJNMMI Radiopharmacy and Chemistry Fluorine-18 6-[18F]fluoronicotinic acid Peptide radiolabeling PET Prosthetic group |
| title | Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules |
| title_full | Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules |
| title_fullStr | Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules |
| title_full_unstemmed | Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules |
| title_short | Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules |
| title_sort | rapid cleavage of 6 18f fluoronicotinic acid prosthetic group governs bt12 glioblastoma xenograft uptake implications for radiolabeling design of biomolecules |
| topic | Fluorine-18 6-[18F]fluoronicotinic acid Peptide radiolabeling PET Prosthetic group |
| url | https://doi.org/10.1186/s41181-025-00368-1 |
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