Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker
Abstract P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized la...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22930-6 |
| _version_ | 1811223629869875200 |
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| author | Pardeep Kumar Riptee Thakur Pratap Chandra Acharya Hosahalli K. Mohan U. N. Pallavi Divya Maheshwari Afsal Mohammed K M Aishwarya Kumar Sridhar Goud Nerella Raman Kumar Joshi Manoj Kumar Chandana Nagaraj |
| author_facet | Pardeep Kumar Riptee Thakur Pratap Chandra Acharya Hosahalli K. Mohan U. N. Pallavi Divya Maheshwari Afsal Mohammed K M Aishwarya Kumar Sridhar Goud Nerella Raman Kumar Joshi Manoj Kumar Chandana Nagaraj |
| author_sort | Pardeep Kumar |
| collection | DOAJ |
| description | Abstract P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized labeled AVT-011 with fluorine-18 (18F) followed by in-vitro and in-vivo analysis. Tosylate AVT-011 precursor was synthesized and characterized by 1H-NMR and 13C-NMR. AVT-011 was labeled with 18F using the nucleophilic substitution method, and a standard set of quality control was performed. The specificity for Pgp was tested in U87MG cells with and without an inhibitor (tariquidar). The biodistribution and in-vivo stability were tested in the small animals (mice). The biodistribution data of [18F]-AVT-011 was extracted from the PET-CT imaging of breast cancer patients (n = 6). The precursor was synthesized with 36 ± 4% yield and 97 ± 2% purity. The labeling was more than 95% with a 42 ± 2% yield, as evaluated by Radio-HPLC. The cell-binding assay showed a specificity of the tracer for Pgp as the uptake increased by twice after blocking the Pgp receptors. The radiotracer showed a hepatorenal excretion pathway for clearance in an animal study. The uptake was higher in the liver, lungs, spleen, and heart at 15 min and decreased at 60 min. The patients' distribution showed similar uptake patterns as observed in the small animals. [18F]AVT-011 was characterized successfully with high radiochemical purity and yield. The in-vitro and in-vivo studies proved its specificity for Pgp and safe for patient use. |
| first_indexed | 2024-04-12T08:36:04Z |
| format | Article |
| id | doaj.art-34d6490243fb45c4b0e676367aff614c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T08:36:04Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-34d6490243fb45c4b0e676367aff614c2022-12-22T03:40:00ZengNature PortfolioScientific Reports2045-23222022-11-0112111110.1038/s41598-022-22930-6Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging markerPardeep Kumar0Riptee Thakur1Pratap Chandra Acharya2Hosahalli K. Mohan3U. N. Pallavi4Divya Maheshwari5Afsal Mohammed K M6Aishwarya Kumar7Sridhar Goud Nerella8Raman Kumar Joshi9Manoj Kumar10Chandana Nagaraj11Department of Neuroimaging and Interventional Radiology, NIMHANSDepartment of Neuroimaging and Interventional Radiology, NIMHANSDepartment of Pharmacy, Tripura University (A Central University)Department of Nuclear Medicine, Sri Shankara Cancer Hospital & Research CentreDepartment of Nuclear Medicine, Sri Shankara Cancer Hospital & Research CentreAvaant ImagingEsente HealthcareDepartment of Neuroimaging and Interventional Radiology, NIMHANSDepartment of Neuroimaging and Interventional Radiology, NIMHANSDepartment of Neuroimaging and Interventional Radiology, NIMHANSDepartment of Neuroimaging and Interventional Radiology, NIMHANSDepartment of Neuroimaging and Interventional Radiology, NIMHANSAbstract P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized labeled AVT-011 with fluorine-18 (18F) followed by in-vitro and in-vivo analysis. Tosylate AVT-011 precursor was synthesized and characterized by 1H-NMR and 13C-NMR. AVT-011 was labeled with 18F using the nucleophilic substitution method, and a standard set of quality control was performed. The specificity for Pgp was tested in U87MG cells with and without an inhibitor (tariquidar). The biodistribution and in-vivo stability were tested in the small animals (mice). The biodistribution data of [18F]-AVT-011 was extracted from the PET-CT imaging of breast cancer patients (n = 6). The precursor was synthesized with 36 ± 4% yield and 97 ± 2% purity. The labeling was more than 95% with a 42 ± 2% yield, as evaluated by Radio-HPLC. The cell-binding assay showed a specificity of the tracer for Pgp as the uptake increased by twice after blocking the Pgp receptors. The radiotracer showed a hepatorenal excretion pathway for clearance in an animal study. The uptake was higher in the liver, lungs, spleen, and heart at 15 min and decreased at 60 min. The patients' distribution showed similar uptake patterns as observed in the small animals. [18F]AVT-011 was characterized successfully with high radiochemical purity and yield. The in-vitro and in-vivo studies proved its specificity for Pgp and safe for patient use.https://doi.org/10.1038/s41598-022-22930-6 |
| spellingShingle | Pardeep Kumar Riptee Thakur Pratap Chandra Acharya Hosahalli K. Mohan U. N. Pallavi Divya Maheshwari Afsal Mohammed K M Aishwarya Kumar Sridhar Goud Nerella Raman Kumar Joshi Manoj Kumar Chandana Nagaraj Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker Scientific Reports |
| title | Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker |
| title_full | Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker |
| title_fullStr | Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker |
| title_full_unstemmed | Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker |
| title_short | Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker |
| title_sort | synthesis characterization and radiosynthesis of fluorine 18 avt 011 as a pgp chemoresistance imaging marker |
| url | https://doi.org/10.1038/s41598-022-22930-6 |
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