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Title: F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET

Abstract

The goal of the proposed work is to develop novel dual-labeled molecular imaging probes for multimodality imaging. Based on small, engineered antibodies called diabodies, these probes will be radioactively tagged with Fluorine-18 for PET imaging, and fused to luciferases for optical (bioluminescence) detection. Performance will be evaluated and validated using a prototype integrated optical-PET imaging system, OPET. Multimodality probes for optical-PET imaging will be based on diabodies that are dually labeled with 18F for PET detection and fused to luciferases for optical imaging. 1) Two sets of fusion proteins will be built, targeting the cell surface markers CEA or HER2. Coelenterazine-based luciferases and variant forms will be evaluated in combination with native substrate and analogs, in order to obtain two distinct probes recognizing different targets with different spectral signatures. 2) Diabody-luciferase fusion proteins will be labeled with 18F using amine reactive [18F]-SFB produced using a novel microwave-assisted, one-pot method. 3) Sitespecific, chemoselective radiolabeling methods will be devised, to reduce the chance that radiolabeling will inactivate either the target-binding properties or the bioluminescence properties of the diabody-luciferase fusion proteins. 4) Combined optical and PET imaging of these dual modality probes will be evaluated and validated in vitro and in vivo usingmore » a prototype integrated optical-PET imaging system, OPET. Each imaging modality has its strengths and weaknesses. Development and use of dual modality probes allows optical imaging to benefit from the localization and quantitation offered by the PET mode, and enhances the PET imaging by enabling simultaneous detection of more than one probe.« less

Authors:
 [1]
  1. Univ. of California, Los Angeles, CA (United States)
Publication Date:
Research Org.:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1060194
Report Number(s):
DOE/SC0001220-1
DOE Contract Number:  
SC0001220
Resource Type:
Technical Report
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 60 APPLIED LIFE SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; Fluorine-18; Antibody; Luciferase; Bioluminescence; Optical Imaging; PET Imaging; Multi-modality Imaging

Citation Formats

Wu, Anna M. F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET. United States: N. p., 2013. Web. doi:10.2172/1060194.
Wu, Anna M. F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET. United States. doi:10.2172/1060194.
Wu, Anna M. Fri . "F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET". United States. doi:10.2172/1060194. https://www.osti.gov/servlets/purl/1060194.
@article{osti_1060194,
title = {F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET},
author = {Wu, Anna M.},
abstractNote = {The goal of the proposed work is to develop novel dual-labeled molecular imaging probes for multimodality imaging. Based on small, engineered antibodies called diabodies, these probes will be radioactively tagged with Fluorine-18 for PET imaging, and fused to luciferases for optical (bioluminescence) detection. Performance will be evaluated and validated using a prototype integrated optical-PET imaging system, OPET. Multimodality probes for optical-PET imaging will be based on diabodies that are dually labeled with 18F for PET detection and fused to luciferases for optical imaging. 1) Two sets of fusion proteins will be built, targeting the cell surface markers CEA or HER2. Coelenterazine-based luciferases and variant forms will be evaluated in combination with native substrate and analogs, in order to obtain two distinct probes recognizing different targets with different spectral signatures. 2) Diabody-luciferase fusion proteins will be labeled with 18F using amine reactive [18F]-SFB produced using a novel microwave-assisted, one-pot method. 3) Sitespecific, chemoselective radiolabeling methods will be devised, to reduce the chance that radiolabeling will inactivate either the target-binding properties or the bioluminescence properties of the diabody-luciferase fusion proteins. 4) Combined optical and PET imaging of these dual modality probes will be evaluated and validated in vitro and in vivo using a prototype integrated optical-PET imaging system, OPET. Each imaging modality has its strengths and weaknesses. Development and use of dual modality probes allows optical imaging to benefit from the localization and quantitation offered by the PET mode, and enhances the PET imaging by enabling simultaneous detection of more than one probe.},
doi = {10.2172/1060194},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2013},
month = {1}
}