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Photoactivatable Fluorescent Tags for Dual-Modality Positron Emission Tomography Optical Imaging


Guillou, Amaury; Nisli, Eda; Klingler, Simon; Linden, Anthony; Holland, Jason P (2022). Photoactivatable Fluorescent Tags for Dual-Modality Positron Emission Tomography Optical Imaging. Journal of Medicinal Chemistry, 65(1):811-823.

Abstract

Fluorescent protein conjugates are vital tools in a wide range of scientific disciplines from basic biochemical research to applications in clinical pathology and intraoperative surgery. We report the synthesis and characterization of photoactivatable fluorophores (PhotoTags) based on the functionalization of coumarin, fluorescein, BODIPY, rhodamine B, and cyanine dyes with a photochemically active aryl azide group. Photochemical labeling experiments using human serum albumin produced fluorescent proteins in high yields under irradiation with ultraviolet light for <15 min. We also synthesized DFO-RhodB-PEG3-ArN3─a photoactivatable compound that can be radiolabeled with 89Zr for applications in optical imaging and positron emission tomography. One-pot 89Zr-radiolabeling and light-induced protein conjugation produced [89Zr]ZrDFO-RhodB-PEG3-azepin-trastuzumab. Proof-of-concept studies in vitro and in vivo confirmed that [89Zr]ZrDFO-RhodB-PEG3-azepin-trastuzumab is a potential dual-modality agent for detecting human epidermal growth factor receptor 2 (HER2/neu) expression. Overall, the PhotoTag technology represents a rapid, synthetically versatile, and user-friendly approach for generating novel protein conjugates.

Abstract

Fluorescent protein conjugates are vital tools in a wide range of scientific disciplines from basic biochemical research to applications in clinical pathology and intraoperative surgery. We report the synthesis and characterization of photoactivatable fluorophores (PhotoTags) based on the functionalization of coumarin, fluorescein, BODIPY, rhodamine B, and cyanine dyes with a photochemically active aryl azide group. Photochemical labeling experiments using human serum albumin produced fluorescent proteins in high yields under irradiation with ultraviolet light for <15 min. We also synthesized DFO-RhodB-PEG3-ArN3─a photoactivatable compound that can be radiolabeled with 89Zr for applications in optical imaging and positron emission tomography. One-pot 89Zr-radiolabeling and light-induced protein conjugation produced [89Zr]ZrDFO-RhodB-PEG3-azepin-trastuzumab. Proof-of-concept studies in vitro and in vivo confirmed that [89Zr]ZrDFO-RhodB-PEG3-azepin-trastuzumab is a potential dual-modality agent for detecting human epidermal growth factor receptor 2 (HER2/neu) expression. Overall, the PhotoTag technology represents a rapid, synthetically versatile, and user-friendly approach for generating novel protein conjugates.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Life Sciences > Molecular Medicine
Life Sciences > Drug Discovery
Uncontrolled Keywords:Drug Discovery, Molecular Medicine
Language:English
Date:13 January 2022
Deposited On:05 Jan 2023 08:52
Last Modified:28 Jun 2024 01:37
Publisher:American Chemical Society (ACS)
ISSN:0022-2623
OA Status:Green
Publisher DOI:https://doi.org/10.1021/acs.jmedchem.1c01899
PubMed ID:34981931
Project Information:
  • : FunderH2020
  • : Grant ID101001734
  • : Project TitlePhotoPHARMA - Light-induced synthesis of protein-drug conjugates for imaging and therapy
  • : FunderH2020
  • : Grant ID676904
  • : Project TitleNanoSCAN - Developing multi-modality nanomedicines for targeted annotation of oncogenic signaling pathways
  • : FunderSwiss National Science Foundation (SNSF)
  • : Grant IDPP00P2_163683
  • : Project Title
  • : FunderSwiss National Science Foundation (SNSF)
  • : Grant IDPP00P2_190093
  • : Project Title