Baseline $[^{18}F]FMISO$ $\mu PET$ as a predictive biomarker for response to $HIF-1\alpha$ inhibition combined with 5-FU chemotherapy in a human colorectal cancer xenograft model

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.

Publication year:2016

Keywords:A1 Journal article

BOF-keylabel:yes

BOF-publication weight:1

CSS-citation score:1

Authors from:Higher Education

Accessibility:Open