English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  In a colorectal cancer xenograft model, we investigated the therapeutic effect of metformin on tumor hypoxia with [ 18 F]flortanidazole ([ 18 F]HX4) small-animal positron emission tomography (μPET). We also assessed the additive effect of metformin on long-term radiotherapy outcome and we studied the potential of [ 18 F]HX4 as a predictive and/or prognostic biomarker within this setup.    Methods  Colo205-bearing mice ( n  = 40) underwent a baseline [ 18 F]HX4 hypoxia μPET/computed tomography (CT) scan. The next day, mice received 100 mg/kg metformin or saline intravenously ( n  = 20/group) and [ 18 F]HX4 was administered intravenously 30 min later, whereupon a second μPET/CT scan was performed to assess changes in tumor hypoxia. Two days later, mice were further divided into four therapy groups ( n  = 10/group): control (1), metformin (2), radiotherapy (3), and metformin + radiotherapy, i.e., combination (4). Then, they received a second dose of metformin (groups 2 and 4) or saline (groups 1 and 3), followed by a single radiotherapy dose of 15 Gy (groups 3 and 4) or sham irradiation (groups 1 and 2) 30 min later. Tumor growth was followed three times a week by caliper measurements to assess the therapeutic outcome.    Results  [ 18 F]HX4 uptake decreased in metformin-treated tumors with a mean intratumoral reduction in [ 18 F]HX4 tumor-to-background ratio (TBR) from 2.53 ± 0.30 to 2.28 ± 0.26 ( p  = 0.04), as opposed to saline treatment (2.56 ± 0.39 to 3.08 ± 0.39;  p  = 0.2). The median tumor doubling time (TDT) was 6, 8, 41, and 43 days in the control, metformin, radiotherapy and combination group, respectively (log-rank  p  < 0.0001), but no metformin-specific therapy effects could be detected. Baseline [ 18 F]HX4 TBR was a negative prognostic biomarker for TDT (hazard ratio, 2.39;  p  = 0.02).    Conclusions  Metformin decreased [ 18 F]HX4 uptake of Colo205-tumors, but had no additive effect on radiotherapy efficacy. Nevertheless, [ 18 F]HX4 holds promise as a prognostic imaging biomarker.

Effects of metformin on tumor hypoxia and radiotherapy efficacy: a [18F]HX4 PET imaging study in colorectal cancer xenografts