Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma
Purpose: N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) for hepatocellular carcinoma (HCC) imaging has been performed in our previous studies, but its radiosynthesis method and stability in vivo need to be improved. Hence, we evaluated the synthesis and biological properties of a simple [18F]-l...
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2021.630452/full |
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| author | Liping Lin Xianhong Xiang Shu Su Shaoyu Liu Ying Xiong Hui Ma Gongjun Yuan Dahong Nie Dahong Nie Ganghua Tang Ganghua Tang |
| author_facet | Liping Lin Xianhong Xiang Shu Su Shaoyu Liu Ying Xiong Hui Ma Gongjun Yuan Dahong Nie Dahong Nie Ganghua Tang Ganghua Tang |
| author_sort | Liping Lin |
| collection | DOAJ |
| description | Purpose: N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) for hepatocellular carcinoma (HCC) imaging has been performed in our previous studies, but its radiosynthesis method and stability in vivo need to be improved. Hence, we evaluated the synthesis and biological properties of a simple [18F]-labeled glutamate analog, [18F]AlF-1,4,7-triazacyclononane-1,4,7-triacetic-acid-2-S-(4-isothiocyanatobenzyl)-l-glutamate ([18F]AlF-NOTA-NSC-GLU), for HCC imaging.Procedures: [18F]AlF-NOTA-NSC-GLU was synthesized via a one-step reaction sequence from NOTA-NSC-GLU. In order to investigate the imaging value of [18F]AlF-NOTA-NSC-GLU in HCC, we conducted positron emission tomography/computed tomography (PET/CT) imaging and competitive binding of [18F]AlF-NOTA-NSC-GLU in human Hep3B tumor-bearing mice. The transport mechanism of [18F]AlF-NOTA-NSC-GLU was determined by competitive inhibition and protein incorporation experiments in vitro.Results: [18F]AlF-NOTA-NSC-GLU was prepared with an overall radiochemical yield of 29.3 ± 5.6% (n = 10) without decay correction within 20 min. In vitro competitive inhibition experiments demonstrated that the Na+-dependent systems XAG-, B0+, ASC, and minor XC- were involved in the uptake of [18F]AlF-NOTA-NSC-GLU, with the Na+-dependent system XAG- possibly playing a more dominant role. Protein incorporation studies of the Hep3B human hepatoma cell line showed almost no protein incorporation. Micro-PET/CT imaging with [18F]AlF-NOTA-NSC-GLU showed good tumor-to-background contrast in Hep3B human hepatoma-bearing mouse models. After [18F]AlF-NOTA-NSC-GLU injection, the tumor-to-liver uptake ratio of [18F]AlF-NOTA-NSC-GLU was 2.06 ± 0.17 at 30 min post-injection. In vivo competitive binding experiments showed that the tumor-to-liver uptake ratio decreased with the addition of inhibitors to block the XAG system.Conclusions: We have successfully synthesized [18F]AlF-NOTA-NSC-GLU as a novel PET tracer with good radiochemical yield and high radiochemical purity. Our findings indicate that [18F]AlF-NOTA-NSC-GLU may be a potential candidate for HCC imaging. Also, a further biological evaluation is underway. |
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| spelling | doaj.art-77c6f5637e3a443ab12eed485fbe9ac32022-12-21T22:45:19ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-04-01910.3389/fchem.2021.630452630452Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular CarcinomaLiping Lin0Xianhong Xiang1Shu Su2Shaoyu Liu3Ying Xiong4Hui Ma5Gongjun Yuan6Dahong Nie7Dahong Nie8Ganghua Tang9Ganghua Tang10Department of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiotherapy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Radiology Intervention and Medical Imaging, Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNanfang PET Center, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaPurpose: N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) for hepatocellular carcinoma (HCC) imaging has been performed in our previous studies, but its radiosynthesis method and stability in vivo need to be improved. Hence, we evaluated the synthesis and biological properties of a simple [18F]-labeled glutamate analog, [18F]AlF-1,4,7-triazacyclononane-1,4,7-triacetic-acid-2-S-(4-isothiocyanatobenzyl)-l-glutamate ([18F]AlF-NOTA-NSC-GLU), for HCC imaging.Procedures: [18F]AlF-NOTA-NSC-GLU was synthesized via a one-step reaction sequence from NOTA-NSC-GLU. In order to investigate the imaging value of [18F]AlF-NOTA-NSC-GLU in HCC, we conducted positron emission tomography/computed tomography (PET/CT) imaging and competitive binding of [18F]AlF-NOTA-NSC-GLU in human Hep3B tumor-bearing mice. The transport mechanism of [18F]AlF-NOTA-NSC-GLU was determined by competitive inhibition and protein incorporation experiments in vitro.Results: [18F]AlF-NOTA-NSC-GLU was prepared with an overall radiochemical yield of 29.3 ± 5.6% (n = 10) without decay correction within 20 min. In vitro competitive inhibition experiments demonstrated that the Na+-dependent systems XAG-, B0+, ASC, and minor XC- were involved in the uptake of [18F]AlF-NOTA-NSC-GLU, with the Na+-dependent system XAG- possibly playing a more dominant role. Protein incorporation studies of the Hep3B human hepatoma cell line showed almost no protein incorporation. Micro-PET/CT imaging with [18F]AlF-NOTA-NSC-GLU showed good tumor-to-background contrast in Hep3B human hepatoma-bearing mouse models. After [18F]AlF-NOTA-NSC-GLU injection, the tumor-to-liver uptake ratio of [18F]AlF-NOTA-NSC-GLU was 2.06 ± 0.17 at 30 min post-injection. In vivo competitive binding experiments showed that the tumor-to-liver uptake ratio decreased with the addition of inhibitors to block the XAG system.Conclusions: We have successfully synthesized [18F]AlF-NOTA-NSC-GLU as a novel PET tracer with good radiochemical yield and high radiochemical purity. Our findings indicate that [18F]AlF-NOTA-NSC-GLU may be a potential candidate for HCC imaging. Also, a further biological evaluation is underway.https://www.frontiersin.org/articles/10.3389/fchem.2021.630452/fullhepatocellular carcinomaPET[18F]AlF-NOTA-NSC-GLUsystem XAG-tumor imaging |
| spellingShingle | Liping Lin Xianhong Xiang Shu Su Shaoyu Liu Ying Xiong Hui Ma Gongjun Yuan Dahong Nie Dahong Nie Ganghua Tang Ganghua Tang Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma Frontiers in Chemistry hepatocellular carcinoma PET [18F]AlF-NOTA-NSC-GLU system XAG- tumor imaging |
| title | Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma |
| title_full | Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma |
| title_fullStr | Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma |
| title_full_unstemmed | Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma |
| title_short | Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma |
| title_sort | biological evaluation of 18f alf nota nsc glu as a positron emission tomography tracer for hepatocellular carcinoma |
| topic | hepatocellular carcinoma PET [18F]AlF-NOTA-NSC-GLU system XAG- tumor imaging |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2021.630452/full |
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