Hybrid multimodal imaging synthons for chemoselective and efficient biomolecule modification with chelator and near-infrared fluorescent cyanine dye

• Verfasst von: Hübner, Ralph [VerfasserIn]
• Verfasst von: Kiedrowski, Valeska von [VerfasserIn]
• Verfasst von: Benkert, Vanessa [VerfasserIn]
• Verfasst von: Wängler, Björn [VerfasserIn]
• Verfasst von: Schirrmacher, Ralf [VerfasserIn]
• Verfasst von: Krämer, Roland [VerfasserIn]
• Verfasst von: Wängler, Carmen [VerfasserIn]
• Titel: Hybrid multimodal imaging synthons for chemoselective and efficient biomolecule modification with chelator and near-infrared fluorescent cyanine dye
• Verf.angabe: Ralph Hübner, Valeska von Kiedrowski, Vanessa Benkert, Björn Wängler, Ralf Schirrmacher, Roland Krämer and Carmen Wängler
• E-Jahr: 2020
• Jahr: 16 September 2020
• Umfang: 14 S.
• Fussnoten: Gesehen am 16.11.2020
• Titel Quelle: Enthalten in: Pharmaceuticals
• Ort Quelle: Basel : MDPI, 2004
• Jahr Quelle: 2020
• Band/Heft Quelle: 13(2020,9) Artikel-Nummer 250, 14 Seiten
• ISSN Quelle: 1424-8247
• DOI: doi:10.3390/ph13090250
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ⁶⁸Ga³⁺
• Sach-SW: chelator
• Sach-SW: click chemistry
• Sach-SW: cyanine dye
• Sach-SW: GRPR affinity
• Sach-SW: multimodal imaging
• Sach-SW: NIR fluorescent dye
• Sach-SW: peptide carrier
• Sach-SW: peptide homodimer
• K10plus-PPN: 1738733122

Abstract

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 68Ga3+. The hybrid multimodal agents were characterized with regard to their logDs, 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.