Title
Baseline <tex>$[^{18}F]FMISO$</tex> <tex>$\mu PET$</tex> as a predictive biomarker for response to <tex>$HIF-1\alpha$</tex> inhibition combined with 5-FU chemotherapy in a human colorectal cancer xenograft model Baseline <tex>$[^{18}F]FMISO$</tex> <tex>$\mu PET$</tex> as a predictive biomarker for response to <tex>$HIF-1\alpha$</tex> inhibition combined with 5-FU chemotherapy in a human colorectal cancer xenograft model
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
,
Subject
Human medicine
Computer. Automation
Source (journal)
Molecular imaging and biology. - Place of publication unknown
Volume/pages
18(2016) :4 , p. 606-616
ISSN
1536-1632
ISI
000379191800016
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Purpose The purpose of this study was to characterize imaging biomarkers for the potential benefit of hypoxia-inducible factor-1 (HIF-1)α inhibition (by PX-12) during 5-fluorouracil (5-FU) chemotherapy in the treatment of colorectal cancer (CRC). Procedures Therapy response to 5-FU ± PX-12 was assessed with baseline [18F]fluoromisonidazole ([18F]FMISO) and longitudinal 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission computed tomography (μPET/CT) in CRC xenograft model (n = 36) during breathing of a hypoxic (10 % O2) or normoxic (21 % O2) atmosphere. Ex vivo, immunohistochemistry was performed. Results Baseline [18F]FMISO uptake and relative tumor volume (RTV) 2 days after 5-FU or 5-FU + PX-12 administration correlated significantly (p ≤ 0.01). Under hypoxic breathing conditions, [18F]FDG uptake (−53.1 ± 8.4 %) and Ki67 expression (−16 %) decreased and RTV stagnated in the 5-FU + PX-12 treatment group, but not in 5-FU alone-treated tumors. Under normoxic breathing, [18F]FDG uptake (−23.5 ± 15.2 % and −72.8 ± 7.1 %) and Ki67 expression (−5 % and −19 %) decreased and RTV stagnated in both the 5-FU and the combination treatment group, respectively. Conclusion Baseline [18F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/d6ddd4/132078.pdf
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