Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells
In this work, a method for the preparation of the highly lipophilic labeling synthon [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was optimized for the radiolabeling of liposomes and human induced pluripotent stem cells (hiPSCs). The aim was to establish a robust and reliable lab...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/7/1097 |
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| author | Andras Polyak Jens P. Bankstahl Karen F. W. Besecke Constantin Hozsa Wiebke Triebert Rajeswara Rao Pannem Felix Manstein Thomas Borcholte Marcus Furch Robert Zweigerdt Robert K. Gieseler Frank M. Bengel Tobias L. Ross |
| author_facet | Andras Polyak Jens P. Bankstahl Karen F. W. Besecke Constantin Hozsa Wiebke Triebert Rajeswara Rao Pannem Felix Manstein Thomas Borcholte Marcus Furch Robert Zweigerdt Robert K. Gieseler Frank M. Bengel Tobias L. Ross |
| author_sort | Andras Polyak |
| collection | DOAJ |
| description | In this work, a method for the preparation of the highly lipophilic labeling synthon [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was optimized for the radiolabeling of liposomes and human induced pluripotent stem cells (hiPSCs). The aim was to establish a robust and reliable labeling protocol for enabling up to one week positron emission tomography (PET) tracing of lipid-based nanomedicines and transplanted or injected cells, respectively. [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was prepared from oxine (8-hydroxyquinoline) and [<sup>89</sup>Zr]Zr(OH)<sub>2</sub>(C<sub>2</sub>O<sub>4</sub>). Earlier introduced liquid–liquid extraction methods were simplified by the optimization of buffering, pH, temperature and reaction times. For quality control, thin-layer chromatography (TLC), size-exclusion chromatography (SEC) and centrifugation were employed. Subsequently, the <sup>89</sup>Zr-complex was incorporated into liposome formulations. PET/CT imaging of <sup>89</sup>Zr-labeled liposomes was performed in healthy mice. Cell labeling was accomplished in PBS using suspensions of 3 × 10<sup>6</sup> hiPSCs, each. [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was synthesized in very high radiochemical yields of 98.7% (96.8% ± 2.8%). Similarly, high internalization rates (≥90%) of [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> into liposomes were obtained over an 18 h incubation period. MicroPET and biodistribution studies confirmed the labeled nanocarriers’ in vivo stability. Human iPSCs incorporated the labeling agent within 30 min with ~50% efficiency. Prolonged PET imaging is an ideal tool in the development of lipid-based nanocarriers for drug delivery and cell therapies. To this end, a reliable and reproducible <sup>89</sup>Zr radiolabeling method was developed and tested successfully in a model liposome system and in hiPSCs alike. |
| first_indexed | 2024-03-10T09:28:25Z |
| format | Article |
| id | doaj.art-8aa27e98e63d476ba7448a4d1cf48e3a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T09:28:25Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8aa27e98e63d476ba7448a4d1cf48e3a2023-11-22T04:42:00ZengMDPI AGPharmaceutics1999-49232021-07-01137109710.3390/pharmaceutics13071097Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and CellsAndras Polyak0Jens P. Bankstahl1Karen F. W. Besecke2Constantin Hozsa3Wiebke Triebert4Rajeswara Rao Pannem5Felix Manstein6Thomas Borcholte7Marcus Furch8Robert Zweigerdt9Robert K. Gieseler10Frank M. Bengel11Tobias L. Ross12Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, GermanyDepartment of Nuclear Medicine, Hannover Medical School, 30625 Hannover, GermanyRodos Biotarget GmbH, Medical Park Hannover, 30625 Hannover, GermanyRodos Biotarget GmbH, Medical Park Hannover, 30625 Hannover, GermanyLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), 30625 Hannover, GermanyRodos Biotarget GmbH, Medical Park Hannover, 30625 Hannover, GermanyLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), 30625 Hannover, GermanyRodos Biotarget GmbH, Medical Park Hannover, 30625 Hannover, GermanyRodos Biotarget GmbH, Medical Park Hannover, 30625 Hannover, GermanyLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), 30625 Hannover, GermanyRodos Biotarget GmbH, Medical Park Hannover, 30625 Hannover, GermanyDepartment of Nuclear Medicine, Hannover Medical School, 30625 Hannover, GermanyDepartment of Nuclear Medicine, Hannover Medical School, 30625 Hannover, GermanyIn this work, a method for the preparation of the highly lipophilic labeling synthon [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was optimized for the radiolabeling of liposomes and human induced pluripotent stem cells (hiPSCs). The aim was to establish a robust and reliable labeling protocol for enabling up to one week positron emission tomography (PET) tracing of lipid-based nanomedicines and transplanted or injected cells, respectively. [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was prepared from oxine (8-hydroxyquinoline) and [<sup>89</sup>Zr]Zr(OH)<sub>2</sub>(C<sub>2</sub>O<sub>4</sub>). Earlier introduced liquid–liquid extraction methods were simplified by the optimization of buffering, pH, temperature and reaction times. For quality control, thin-layer chromatography (TLC), size-exclusion chromatography (SEC) and centrifugation were employed. Subsequently, the <sup>89</sup>Zr-complex was incorporated into liposome formulations. PET/CT imaging of <sup>89</sup>Zr-labeled liposomes was performed in healthy mice. Cell labeling was accomplished in PBS using suspensions of 3 × 10<sup>6</sup> hiPSCs, each. [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was synthesized in very high radiochemical yields of 98.7% (96.8% ± 2.8%). Similarly, high internalization rates (≥90%) of [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> into liposomes were obtained over an 18 h incubation period. MicroPET and biodistribution studies confirmed the labeled nanocarriers’ in vivo stability. Human iPSCs incorporated the labeling agent within 30 min with ~50% efficiency. Prolonged PET imaging is an ideal tool in the development of lipid-based nanocarriers for drug delivery and cell therapies. To this end, a reliable and reproducible <sup>89</sup>Zr radiolabeling method was developed and tested successfully in a model liposome system and in hiPSCs alike.https://www.mdpi.com/1999-4923/13/7/1097nanoparticlesliposomescell labelingimagingPETnanomedicine |
| spellingShingle | Andras Polyak Jens P. Bankstahl Karen F. W. Besecke Constantin Hozsa Wiebke Triebert Rajeswara Rao Pannem Felix Manstein Thomas Borcholte Marcus Furch Robert Zweigerdt Robert K. Gieseler Frank M. Bengel Tobias L. Ross Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells Pharmaceutics nanoparticles liposomes cell labeling imaging PET nanomedicine |
| title | Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells |
| title_full | Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells |
| title_fullStr | Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells |
| title_full_unstemmed | Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells |
| title_short | Simplified <sup>89</sup>Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells |
| title_sort | simplified sup 89 sup zr labeling protocol of oxine 8 hydroxyquinoline enabling prolonged tracking of liposome based nanomedicines and cells |
| topic | nanoparticles liposomes cell labeling imaging PET nanomedicine |
| url | https://www.mdpi.com/1999-4923/13/7/1097 |
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