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

Journal Article · · Bioconjugate Chemistry
DOI:https://doi.org/10.1021/bc500415x· OSTI ID:1345182
 [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)
+ Show Author Affiliations

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.

Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
SC0008384
OSTI ID:
1345182
Journal Information:
Bioconjugate Chemistry, Vol. 25, Issue 12; ISSN 1043-1802
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 60 works
Citation information provided by
Web of Science

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Cited By (18)

Antibody Fragment and Affibody ImmunoPET Imaging Agents: Radiolabelling Strategies and Applications journal November 2018
AAZTA: An Ideal Chelating Agent for the Development of 44 Sc PET Imaging Agents journal January 2017
47Sc as useful β–-emitter for the radiotheragnostic paradigm: a comparative study of feasible production routes text January 2017
Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry journal September 2015
Antibody‐Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases journal June 2018
Production and separation of 43Sc for radiopharmaceutical purposes journal November 2017
Clinically Relevant Radioactive Dose Formulation of 177 Lu-Labeled Cetuximab-Fab Fragment for Potential Use in Cancer Theranostics journal January 2018
Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application journal November 2018
44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations journal May 2016
Image quality analysis of 44Sc on two preclinical PET scanners: a comparison to 68Ga journal March 2020
PET and SPECT imaging of melanoma: the state of the art journal October 2017
47Sc as useful β–-emitter for the radiotheragnostic paradigm: a comparative study of feasible production routes journal June 2017
AAZTA: An Ideal Chelating Agent for the Development of 44 Sc PET Imaging Agents journal January 2017
Targeting of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein with a Technetium-99m Imaging Probe journal June 2018
Direct fluorine-18 labeling of heat-sensitive biomolecules for positron emission tomography imaging using the Al18F-RESCA method journal September 2018
Production and separation of 43Sc for radiopharmaceutical purposes text January 2017
44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations text January 2016
Al18F-Labeling Of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging journal January 2017

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