Imperial College London

ProfessorEricAboagye

Faculty of MedicineDepartment of Surgery & Cancer

Professor
 
 
 
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Contact

 

+44 (0)20 3313 3759eric.aboagye

 
 
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Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
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Location

 

GN1Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Braga:2020:10.3390/cancers12061703,
author = {Braga, M and Kaliszczak, M and Carroll, L and Schug, ZT and Heinzmann, K and Baxan, N and Benito, A and Valbuena, GN and Stribbling, S and Beckley, A and Mackay, G and Mauri, F and Latigo, J and Barnes, C and Keun, H and Gottlieb, E and Aboagye, EO},
doi = {10.3390/cancers12061703},
journal = {Cancers (Basel)},
title = {Tracing nutrient flux following monocarboxylate transporter-1 inhibition with AZD3965.},
url = {http://dx.doi.org/10.3390/cancers12061703},
volume = {12},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The monocarboxylate transporter 1 (MCT1) is a key element in tumor cell metabolism and inhibition of MCT1 with AZD3965 is undergoing clinical trials. We aimed to investigate nutrient fluxes associated with MCT1 inhibition by AZD3965 to identify possible biomarkers of drug action. We synthesized an 18F-labeled lactate analogue, [18F]-S-fluorolactate ([18F]-S-FL), that was used alongside [18F]fluorodeoxyglucose ([18F]FDG), and 13C-labeled glucose and lactate, to investigate the modulation of metabolism with AZD3965 in diffuse large B-cell lymphoma models in NOD/SCID mice. Comparative analysis of glucose and lactate-based probes showed a preference for glycolytic metabolism in vitro, whereas in vivo, both glucose and lactate were used as metabolic fuel. While intratumoral L-[1-13C]lactate and [18F]-S-FL were unchanged or lower at early (5 or 30 min) timepoints, these variables were higher compared to vehicle controls at 4 h following treatment with AZD3965, which indicates that inhibition of MCT1-mediated lactate import is reversed over time. Nonetheless, AZD3965 treatment impaired DLBCL tumor growth in mice. This was hypothesized to be a consequence of metabolic strain, as AZD3965 treatment showed a reduction in glycolytic intermediates and inhibition of the TCA cycle likely due to downregulated PDH activity. Glucose ([18F]FDG and D-[13C6]glucose) and lactate-based probes ([18F]-S-FL and L-[1-13C]lactate) can be successfully used as biomarkers for AZD3965 treatment.
AU - Braga,M
AU - Kaliszczak,M
AU - Carroll,L
AU - Schug,ZT
AU - Heinzmann,K
AU - Baxan,N
AU - Benito,A
AU - Valbuena,GN
AU - Stribbling,S
AU - Beckley,A
AU - Mackay,G
AU - Mauri,F
AU - Latigo,J
AU - Barnes,C
AU - Keun,H
AU - Gottlieb,E
AU - Aboagye,EO
DO - 10.3390/cancers12061703
PY - 2020///
SN - 2072-6694
TI - Tracing nutrient flux following monocarboxylate transporter-1 inhibition with AZD3965.
T2 - Cancers (Basel)
UR - http://dx.doi.org/10.3390/cancers12061703
UR - https://www.ncbi.nlm.nih.gov/pubmed/32604836
UR - https://www.mdpi.com/2072-6694/12/6/1703
UR - http://hdl.handle.net/10044/1/80351
VL - 12
ER -