| Autor: |
De Bruycker, Sven, Vangestel, Christel, van den Wyngaert, Tim, Pauwels, Patrick, Wyffels, Leonie, Staelens, Steven, Stroobants, Sigrid |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
The Journal of nuclear medicine |
| ISSN: |
0161-5505 |
| Popis: |
Metformin may improve tumor oxygenation and thus radiotherapy response, but imaging biomarkers for selection of suitable patients are still under investigation. First, we assessed the effect of acute metformin administration on non-small cell lung cancer (NSCLC) xenograft tumor hypoxia using positron emission tomography (PET) imaging with the hypoxia tracer 18F-flortanidazole (18F-HX4). Second, we verified the effect of a single dose of metformin prior to radiotherapy on long-term treatment outcome. Third, we examined the potential of baseline 18F-HX4 as a prognostic and/or predictive biomarker for treatment response. Methods: A549 tumor-bearing mice underwent a 18F-HX4 PET/computed tomography (CT) scan to determine baseline tumor hypoxia. The next day, mice received an intravenous (IV) injection of 100 mg/kg metformin. 18F-HX4 was administered IV 30 min later and a second PET/CT scan was performed to assess changes in tumor hypoxia. Two days later, mice were divided into three therapy groups: controls (group 1), radiotherapy (group 2), and metformin+radiotherapy (group 3). Animals received saline (groups 1-2) or 100 mg/kg metformin (group 3) IV, followed by a single radiotherapy dose of 10 Gy (groups 2-3) or sham irradiation (group 1) 30 min later. Tumor growth was monitored triweekly by caliper measurement and relative tumor volumes (RTV=Vtime x/Vbaseline) were calculated. The tumor doubling time (TDT), i.e. the time to reach 2× the pre-irradiation tumor volume, was defined as the endpoint. Results: Thirty min post-metformin treatment, 18F-HX4 demonstrated a significant change in tumor hypoxia with a mean intratumoral reduction in 18F-HX4 tumor-to-background ratio (TBR) from 3.21±0.13 to 2.87±0.13 (P = 0.0001). Overall, RTV over time differed across treatment groups (p |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
