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• W4361959204 abstract "<div>Abstract<p><b>Purpose:</b> Conventional anticancer treatments are often impaired by the presence of hypoxia. TH-302 selectively targets hypoxic tumor regions, where it is converted into a cytotoxic agent. This study assessed the efficacy of the combination treatment of TH-302 and radiotherapy in two preclinical tumor models. The effect of oxygen modification on the combination treatment was evaluated and the effect of TH-302 on the hypoxic fraction (HF) was monitored using [¹⁸F]HX4-PET imaging and pimonidazole IHC stainings.</p><p><b>Experimental Design:</b> Rhabdomyosarcoma R1 and H460 NSCLC tumor-bearing animals were treated with TH-302 and radiotherapy (8 Gy, single dose). The tumor oxygenation status was altered by exposing animals to carbogen (95% oxygen) and nicotinamide, 21% or 7% oxygen breathing during the course of the treatment. Tumor growth and treatment toxicity were monitored until the tumor reached four times its start volume (T4×SV).</p><p><b>Results:</b> Both tumor models showed a growth delay after TH-302 treatment, which further increased when combined with radiotherapy (enhancement ratio rhabdomyosarcoma 1.23; H460 1.49). TH-302 decreases the HF in both models, consistent with its hypoxia-targeting mechanism of action. Treatment efficacy was dependent on tumor oxygenation; increasing the tumor oxygen status abolished the effect of TH-302, whereas enhancing the HF enlarged TH-302′s therapeutic effect. An association was observed in rhabdomyosarcoma tumors between the pretreatment HF as measured by [¹⁸F]HX4-PET imaging and the T4×SV.</p><p><b>Conclusions:</b> The combination of TH-302 and radiotherapy is promising and warrants clinical testing, preferably guided by the companion biomarker [¹⁸F]HX4 hypoxia PET imaging for patient selection. <i>Clin Cancer Res; 21(13); 2984–92. ©2015 AACR</i>.</p></div>" @default.
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• W4361959204 date "2023-03-31" @default.
• W4361959204 modified "2023-09-23" @default.
• W4361959204 title "Data from TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [¹⁸F]HX4 Hypoxia PET Imaging" @default.
• W4361959204 doi "https://doi.org/10.1158/1078-0432.c.6523374" @default.
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