Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye
The development of hybrid multimodal imaging synthons (MIS), carrying in addition to a chelator for radiometal labeling also a near-infrared (NIR) fluorescent cyanine dye was the aim of this work. The MIS should be introducible into biomolecules of choice via an efficient and chemoselective click ch...
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MDPI AG
2020-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/9/250 |
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| author | Ralph Hübner Valeska von Kiedrowski Vanessa Benkert Björn Wängler Ralf Schirrmacher Roland Krämer Carmen Wängler |
| author_facet | Ralph Hübner Valeska von Kiedrowski Vanessa Benkert Björn Wängler Ralf Schirrmacher Roland Krämer Carmen Wängler |
| author_sort | Ralph Hübner |
| collection | DOAJ |
| description | The development of hybrid multimodal imaging synthons (MIS), carrying in addition to a chelator for radiometal labeling also a near-infrared (NIR) fluorescent cyanine dye was the aim of this work. The MIS should be introducible into biomolecules of choice via an efficient and chemoselective click chemistry reaction. After chemical optimization, a successful synthetic strategy towards such hybrid MIS was developed, based on solid phase-based synthesis techniques and applying different near-infrared fluorescent cyanine dyes. The developed hybrid agents were shown to be easily introducible into a model homobivalent peptidic gastrin-releasing peptide receptor- (GRPR)-specific carrier without forming any side products and the MIS as well as their bioconjugates were radiolabeled with the positron-emitter <sup>68</sup>Ga<sup>3+</sup>. The hybrid multimodal agents were characterized with regard to their log<i><sub>D</sub></i>s, GRPR target affinities and photophysical characteristics. It could be shown that the properties of the bioconjugates were not per se affected by the introduction of the MIS but that the cyanine dye used and specifically the number of comprised negative charges per dye molecule can have a considerable influence on target receptor binding. Thus, the molecular toolbox described here enables the synthesis of tailored hybrid multimodal imaging synthons for biomolecule modification, meeting the specific need and envisioned application of the combined imaging agent. |
| first_indexed | 2024-03-10T16:16:41Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T16:16:41Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-0d79519c77a746e3ac8b11d30bdf05982023-11-20T13:58:26ZengMDPI AGPharmaceuticals1424-82472020-09-0113925010.3390/ph13090250Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine DyeRalph Hübner0Valeska von Kiedrowski1Vanessa Benkert2Björn Wängler3Ralf Schirrmacher4Roland Krämer5Carmen Wängler6Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyMolecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyInstitute of Inorganic Chemistry, Heidelberg University, Im Neuenheimer Feld 274, 69120 Heidelberg, GermanyMolecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyDepartment of Oncology, Division of Oncological Imaging, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, CanadaInstitute of Inorganic Chemistry, Heidelberg University, Im Neuenheimer Feld 274, 69120 Heidelberg, GermanyBiomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyThe development of hybrid multimodal imaging synthons (MIS), carrying in addition to a chelator for radiometal labeling also a near-infrared (NIR) fluorescent cyanine dye was the aim of this work. The MIS should be introducible into biomolecules of choice via an efficient and chemoselective click chemistry reaction. After chemical optimization, a successful synthetic strategy towards such hybrid MIS was developed, based on solid phase-based synthesis techniques and applying different near-infrared fluorescent cyanine dyes. The developed hybrid agents were shown to be easily introducible into a model homobivalent peptidic gastrin-releasing peptide receptor- (GRPR)-specific carrier without forming any side products and the MIS as well as their bioconjugates were radiolabeled with the positron-emitter <sup>68</sup>Ga<sup>3+</sup>. The hybrid multimodal agents were characterized with regard to their log<i><sub>D</sub></i>s, GRPR target affinities and photophysical characteristics. It could be shown that the properties of the bioconjugates were not per se affected by the introduction of the MIS but that the cyanine dye used and specifically the number of comprised negative charges per dye molecule can have a considerable influence on target receptor binding. Thus, the molecular toolbox described here enables the synthesis of tailored hybrid multimodal imaging synthons for biomolecule modification, meeting the specific need and envisioned application of the combined imaging agent.https://www.mdpi.com/1424-8247/13/9/250chelatorclick chemistrycyanine dye<sup>68</sup>Ga<sup>3+</sup>GRPR affinitymultimodal imaging |
| spellingShingle | Ralph Hübner Valeska von Kiedrowski Vanessa Benkert Björn Wängler Ralf Schirrmacher Roland Krämer Carmen Wängler Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye Pharmaceuticals chelator click chemistry cyanine dye <sup>68</sup>Ga<sup>3+</sup> GRPR affinity multimodal imaging |
| title | Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye |
| title_full | Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye |
| title_fullStr | Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye |
| title_full_unstemmed | Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye |
| title_short | Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye |
| title_sort | hybrid multimodal imaging synthons for chemoselective and efficient biomolecule modification with chelator and near infrared fluorescent cyanine dye |
| topic | chelator click chemistry cyanine dye <sup>68</sup>Ga<sup>3+</sup> GRPR affinity multimodal imaging |
| url | https://www.mdpi.com/1424-8247/13/9/250 |
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