Sven De Bruycker1, Christel Vangestel1,2, Tim Van den Wyngaert1,2, Leonie Wyffels1,2, An Wouters3, Patrick Pauwels3, Steven Staelens1, Sigrid Stroobants4,5. 1. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium. 2. Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium. 3. Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium. 4. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium. sigrid.stroobants@uza.be. 5. Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium. sigrid.stroobants@uza.be.
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 [(18)F]fluoromisonidazole ([(18)F]FMISO) and longitudinal 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]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 [(18)F]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, [(18)F]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, [(18)F]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 [(18)F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.
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 [(18)F]fluoromisonidazole ([(18)F]FMISO) and longitudinal 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]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 [(18)F]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, [(18)F]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, [(18)F]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 [(18)F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.
Authors: Sarah J Welsh; Ryan R Williams; Anne Birmingham; David J Newman; D Lynn Kirkpatrick; Garth Powis Journal: Mol Cancer Ther Date: 2003-03 Impact factor: 6.261
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Authors: Petra Georg; Piotr Andrzejewski; Pascal Baltzer; Michaela Daniel; Wolfgang Wadsak; Markus Mitterhauser; Alina Sturdza; Katarina Majercakova; Georgios Karanikas; Richard Pötter; Marcus Hacker; Thomas Helbich; Dietmar Georg; Katja Pinker Journal: Mol Imaging Biol Date: 2018-02 Impact factor: 3.488
Authors: Sven De Bruycker; Christel Vangestel; Steven Staelens; Tim Van den Wyngaert; Sigrid Stroobants Journal: Contrast Media Mol Imaging Date: 2018-10-18 Impact factor: 3.161