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Title: Matching the decay half-life with the biological half-life: ImmunoPET imaging with 44 Sc-labeled Cetuximab Fab fragment

Abstract

Scandium-44 (t 1/2 = 3.9 h) is a relatively new radioisotope of potential interest for use in clinical positron emission tomography (PET). Herein, we report, for the first time, the room-temperature radiolabeling of proteins with 44Sc for in vivo PET imaging. For this purpose, the Fab fragment of Cetuximab, a monoclonal antibody that binds with high affinity to epidermal growth factor receptor (EGFR), was generated and conjugated with N-[(R)-2-amino-3-( para-isothiocyanato-phenyl)propyl]- trans-(S,S)-cyclohexane-1,2-diamine- N,N,N',N'',N''-pentaacetic acid (CHX-A"-DTPA). The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and mass spectrometry. The potential of the bioconjugate for PET imaging of EGFR expression in human glioblastoma (U87MG) tumor-bearing mice was investigated after 44Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of ~12% ID/g at 4 h postinjection) of 44Sc–CHX-A"-DTPA–Cetuximab-Fab with excellent tumor-to-background ratio, which might allow for same day PET imaging in future clinical studies. Immunofluorescence staining was conducted to correlate tracer uptake in the tumor and normal tissues with EGFR expression. As a result, this successful strategy for immunoPET imaging of EGFR expression using 44Sc–CHX-''-DTPA–Cetuximab-Fab can make clinically translatable advances to select the right population of patients for EGFR-targeted therapy and also to monitor the therapeutic efficacy of anti-EGFR treatments.

Authors:
 [1];  [2];  [2];  [2];  [2];  [2];  [3]
  1. Univ. of Wisconsin, Madison, WI (United States); Bhabha Atomic Research Centre, Mumbai (India)
  2. Univ. of Wisconsin, Madison, WI (United States)
  3. Univ. of Wisconsin, Madison, WI (United States); Univ. of Wisconsin Carbone Cancer Center, Madison, WI (United States)
Publication Date:
Research Org.:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1345182
Grant/Contract Number:  
SC0008384
Resource Type:
Accepted Manuscript
Journal Name:
Bioconjugate Chemistry
Additional Journal Information:
Journal Volume: 25; Journal Issue: 12; Journal ID: ISSN 1043-1802
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY

Citation Formats

Chakravarty, Rubel, Goel, Shreya, Valdovinos, Hector F., Hernandez, Reinier, Hong, Hao, Nickles, Robert J., and Cai, Weibo. Matching the decay half-life with the biological half-life: ImmunoPET imaging with 44 Sc-labeled Cetuximab Fab fragment. United States: N. p., 2014. Web. doi:10.1021/bc500415x.
Chakravarty, Rubel, Goel, Shreya, Valdovinos, Hector F., Hernandez, Reinier, Hong, Hao, Nickles, Robert J., & Cai, Weibo. Matching the decay half-life with the biological half-life: ImmunoPET imaging with 44 Sc-labeled Cetuximab Fab fragment. United States. doi:10.1021/bc500415x.
Chakravarty, Rubel, Goel, Shreya, Valdovinos, Hector F., Hernandez, Reinier, Hong, Hao, Nickles, Robert J., and Cai, Weibo. Tue . "Matching the decay half-life with the biological half-life: ImmunoPET imaging with 44 Sc-labeled Cetuximab Fab fragment". United States. doi:10.1021/bc500415x. https://www.osti.gov/servlets/purl/1345182.
@article{osti_1345182,
title = {Matching the decay half-life with the biological half-life: ImmunoPET imaging with 44 Sc-labeled Cetuximab Fab fragment},
author = {Chakravarty, Rubel and Goel, Shreya and Valdovinos, Hector F. and Hernandez, Reinier and Hong, Hao and Nickles, Robert J. and Cai, Weibo},
abstractNote = {Scandium-44 (t1/2 = 3.9 h) is a relatively new radioisotope of potential interest for use in clinical positron emission tomography (PET). Herein, we report, for the first time, the room-temperature radiolabeling of proteins with 44Sc for in vivo PET imaging. For this purpose, the Fab fragment of Cetuximab, a monoclonal antibody that binds with high affinity to epidermal growth factor receptor (EGFR), was generated and conjugated with N-[(R)-2-amino-3-(para-isothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N'',N''-pentaacetic acid (CHX-A"-DTPA). The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and mass spectrometry. The potential of the bioconjugate for PET imaging of EGFR expression in human glioblastoma (U87MG) tumor-bearing mice was investigated after 44Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of ~12% ID/g at 4 h postinjection) of 44Sc–CHX-A"-DTPA–Cetuximab-Fab with excellent tumor-to-background ratio, which might allow for same day PET imaging in future clinical studies. Immunofluorescence staining was conducted to correlate tracer uptake in the tumor and normal tissues with EGFR expression. As a result, this successful strategy for immunoPET imaging of EGFR expression using 44Sc–CHX-''-DTPA–Cetuximab-Fab can make clinically translatable advances to select the right population of patients for EGFR-targeted therapy and also to monitor the therapeutic efficacy of anti-EGFR treatments.},
doi = {10.1021/bc500415x},
journal = {Bioconjugate Chemistry},
number = 12,
volume = 25,
place = {United States},
year = {2014},
month = {11}
}

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Works referencing / citing this record:

AAZTA: An Ideal Chelating Agent for the Development of 44 Sc PET Imaging Agents
journal, January 2017

  • Nagy, Gábor; Szikra, Dezső; Trencsényi, György
  • Angewandte Chemie International Edition, Vol. 56, Issue 8
  • DOI: 10.1002/anie.201611207