Imperial College London

ProfessorEricAboagye

Faculty of MedicineDepartment of Surgery & Cancer

Professor
 
 
 
//

Contact

 

+44 (0)20 3313 3759eric.aboagye

 
 
//

Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
//

Location

 

GN1Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Heinzmann:2018:10.2967/jnumed.118.209304,
author = {Heinzmann, K and Nguyen, Q-D and Honess, D and Smith, D-M and Stribbling, S and Brickute, D and Barnes, C and Griffiths, J and Aboagye, E},
doi = {10.2967/jnumed.118.209304},
journal = {Journal of Nuclear Medicine},
pages = {1558--1565},
title = {Depicting changes in tumor biology in response to cetuximab mono- or combination therapy by apoptosis and proliferation imaging using 18F-ICMT-11 and 3’-Deoxy-3’-[18F]Fluorothymidine (18F-FLT) PET},
url = {http://dx.doi.org/10.2967/jnumed.118.209304},
volume = {59},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Imaging biomarkers must demonstrate their value in monitoring treatment. Two PET tracers, the caspase-3/7–specific isatin-5-sulfonamide 18F-ICMT-11 (18F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluoro-phenoxymethyl)-pyrrolidine-1-sulfonyl)isatin) and 18F-FLT (3′-deoxy-3′-18F-fluorothymidine), were used to detect early treatment-induced changes in tumor biology and determine whether any of these changes indicate a response to cetuximab, administered as monotherapy or combination therapy with gemcitabine. Methods: In mice bearing cetuximab-sensitive H1975 tumors (non–small lung cancer), the effects of single or repeated doses of the antiepidermal growth factor receptor antibody cetuximab (10 mg/kg on day 1 only or on days 1 and 2) or a single dose of gemcitabine (125 mg/kg on day 2) were investigated by 18F-ICMT-11 or 18F-FLT on day 3. Imaging was also performed after 2 doses of cetuximab (days 1 and 2) in mice bearing cetuximab-insensitive HCT116 tumors (colorectal cancer). For imaging–histology comparison, tumors were evaluated for proliferation (Ki-67 and thymidine kinase 1 [TK1]), cell death (cleaved caspase-3 and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling [TUNEL]), and target engagement (epidermal growth factor receptor expression) by immunohistochemistry, immunofluorescence, and immunoblotting, respectively. Tumor and plasma were analyzed for thymidine and gemcitabine metabolites by liquid chromatography–mass spectrometry. Results: Retention of both tracers was sensitive to cetuximab in H1975 tumors. 18F-ICMT-11 uptake and ex vivo cleaved caspase-3 staining notably increased in tumors treated with repeated doses of cetuximab (75%) and combination treatment (46%). Although a single dose of cetuximab was insufficient to induce apoptosis, it did affect proliferation. Significant reductions in tumor 18F-FLT uptake (44%–50%; P < 0.001) induce
AU - Heinzmann,K
AU - Nguyen,Q-D
AU - Honess,D
AU - Smith,D-M
AU - Stribbling,S
AU - Brickute,D
AU - Barnes,C
AU - Griffiths,J
AU - Aboagye,E
DO - 10.2967/jnumed.118.209304
EP - 1565
PY - 2018///
SN - 1535-5667
SP - 1558
TI - Depicting changes in tumor biology in response to cetuximab mono- or combination therapy by apoptosis and proliferation imaging using 18F-ICMT-11 and 3’-Deoxy-3’-[18F]Fluorothymidine (18F-FLT) PET
T2 - Journal of Nuclear Medicine
UR - http://dx.doi.org/10.2967/jnumed.118.209304
UR - http://hdl.handle.net/10044/1/58982
VL - 59
ER -