Article (Scientific journals)
Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of 2 Epidermal Growth Factor Receptor Over-Expressing Tumors.
Goux, Marine; Becker, Guillaume; Gorré, Harmony et al.
2017In Bioconjugate Chemistry, 28 (9), p. 2361-2371
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Keywords :
EGFR; Nanofitin; fluorine 18; microPET; MRI; Imaging
Abstract :
[en] Epidermal growth-factor receptor (EGFR) is involved in cell growth and proliferation and is over-expressed in malignant tissues. Although anti-EGFR-based immunotherapy became a standard of care for patients with EGFR-positive tumors, this strategy of addressing cancer tumors by targeting EGFR with monoclonal antibodies is less-developed for patient diagnostic and monitoring. Indeed, antibodies exhibit a slow blood clearance, which is detrimental for positron emission tomography (PET) imaging. New molecular probes are proposed to overcome such limitations for patient monitoring, making use of low-molecular-weight protein scaffolds as alternatives to antibodies, such as Nanofitins with better pharmacokinetic profiles. Anti-EGFR Nanofitin B10 was reformatted by genetic engineering to exhibit a unique cysteine moiety at its C-terminus, which allows the development of a fast and site-specific radiolabeling procedure with 18F−4-fluorobenzamido-N-ethylamino-maleimide (18F−FBEM). The in vivo tumor targeting and imaging profile of the anti-EGFR Cys−B10 Nanofitin was investigated in a double-tumor xenograft model by static small-animal PET at 2 h after tail-vein injection of the radiolabeled Nanofitin 18F−FBEM−Cys−B10. The image showed that the EGFR- positive tumor (A431) is clearly delineated in comparison to the EGFR-negative tumor (H520) with a significant tumor-to-background contrast. 18F−FBEM−Cys−B10 demonstrated a significantly higher retention in A431 tumors than in H520 tumors at 2.5 h post-injection with a A431-to-H520 uptake ratio of 2.53 ± 0.18 and a tumor-to-blood ratio of 4.55 ± 0.63. This study provides the first report of Nanofitin scaffold used as a targeted PET radiotracer for in vivo imaging of EGFR-positive tumor, with the anti-EGFR B10 Nanofitin used as proof-of-concept. The fast generation of specific Nanofitins via a fully in vitro selection process, together with the excellent imaging features of the Nanofitin scaffold, could facilitate the development of valuable PET-based companion diagnostics.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Goux, Marine
Becker, Guillaume ;  Université de Liège > Centre de recherches du cyclotron
Gorré, Harmony
Dammicco, Sylvestre ;  Université de Liège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
Desselle, Ariane
Egrise, Dominique
Leroi, Natacha ;  Université de Liège > Département des sciences cliniques > Radiothérapie
Lallemand, François  ;  Université de Liège > Département des sciences cliniques > Radiothérapie
Bahri, Mohamed Ali  ;  Université de Liège > Centre de Recherches du Cyclotron
Doumont, Gilles
Plenevaux, Alain  ;  Université de Liège > Département de chimie (sciences) > Département de chimie (sciences)
Cinier, Mathieu
Luxen, André ;  Université de Liège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
More authors (3 more) Less
Language :
English
Title :
Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of 2 Epidermal Growth Factor Receptor Over-Expressing Tumors.
Publication date :
21 August 2017
Journal title :
Bioconjugate Chemistry
ISSN :
1043-1802
eISSN :
1520-4812
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Volume :
28
Issue :
9
Pages :
2361-2371
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 19 October 2017

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