ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2013
18F-EF5 PET imaging as an early response biomarker for the hypoxia-activated prodrug SN30000 combined with radiation treatment in a non-small cell lung cancer xenograft model.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- Combined Oxygen-Enhanced MRI and Perfusion Imaging Detect Hypoxia Modification from Banoxantrone and Atovaquone and Track Their Differential Mechanisms of Action.Cancer research communications · 2024Article
- Medicinal Chemistry of Drugs withJournal of medicinal chemistry · 2024Review
- Oxygen-Guided Radiation Therapy.International journal of radiation oncology, biology, physics · 2019Article
- Hypoxia-targeted drug delivery.Chemical Society reviews · 2019Review
- Monitoring the Early Response of Fulvestrant Plus Tanshinone IIA Combination Therapy to Estrogen Receptor-Positive Breast Cancer by LongitudinalContrast media & molecular imaging · 2019Article
- Schedule-dependent potentiation of chemotherapy drugs by the hypoxia-activated prodrug SN30000.Cancer biology & therapy · 2019Article
- Molecular mechanisms of hypoxia in cancer.Clinical and translational imaging · 2017Review
- Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs.Cancer chemotherapy and pharmacology · 2016Review
- Article
- Molecular imaging of hypoxia in non-small-cell lung cancer.European journal of nuclear medicine and molecular imaging · 2015Review
- Optimizing hypoxia detection and treatment strategies.Seminars in nuclear medicine · 2015Review
- F-18 fluoromisonidazole for imaging tumor hypoxia: imaging the microenvironment for personalized cancer therapy.Seminars in nuclear medicine · 2015Review
- 18F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical Tumor Models.PloS one · 2015Article
- PET probes beyond (18)F-FDG.Journal of biomedical research · 2014Review
- Comparison of the Hypoxia PET Tracer (18)F-EF5 to Immunohistochemical Marker EF5 in 3 Different Human Tumor Xenograft Models.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2014Article
- Isotopic labeling experiments that elucidate the mechanism of DNA strand cleavage by the hypoxia-selective antitumor agent 1,2,4-benzotriazine 1,4-di-N-oxide.Chemical research in toxicology · 2014Article
- Evaluation of repeated [(18)F]EF5 PET/CT scans and tumor growth rate in experimental head and neck carcinomas.EJNMMI research · 2014Article
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9 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledHypoxia is a significant therapeutic problem for solid tumors because hypoxic cells are treatment-resistant and more aggressive. Hypoxia-activated prodrugs such as SN30000 use a mechanism of activation in hypoxic cells similar to that of 2-nitroimidazole hypoxia PET tracers. Therefore, we have evaluated the usefulness of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-(18)F-pentafluoropropyl)-acetamide ((18)F-EF5) PET to monitor and predict tumor response to SN30000 plus radiation treatment (RT).
methodsHuman non-small cell lung cancer xenografts (H460) in athymic rats were imaged with (18)F-EF5 PET before and after treatment with SN30000 (90 mg/kg), with or without 15-Gy RT. The feasibility of imaging early changes in hypoxia in response to SN30000 was examined 24 h after treatment, followed by ex vivo γ-counting and immunohistochemical examination to study drug-induced apoptosis. Subsequently, the therapeutic effects of SN30000 with or without RT were evaluated in tumor growth delay studies and compared with early treatment-induced changes observed by (18)F-EF5 PET. Changes in tumor hemoglobin oxygen saturation as a function of time after treatment measured by optical spectroscopy were compared with PET data.
resultsThe uptake of (18)F-EF5 was significantly lower in SN30000-treated tumors than in saline controls 24 h after treatment (mean standardized uptake value, 0.44 ± 0.08 vs. 0.56 ± 0.08 for control group; P < 0.05). Apoptosis was significantly higher in SN30000-treated tumors than in controls. Early treatment-induced changes in (18)F-EF5 uptake were indicative of tumor response in growth delay studies at the group level. SN30000 plus RT significantly decreased (18)F-EF5 uptake relative to baseline and resulted in complete tumor remission in 5 of 7 animals. SN30000 alone decreased (18)F-EF5 uptake, generally in tumors with high initial standardized uptake values, and showed a minor tumor growth delay effect. The changes induced by SN30000 with or without RT in (18)F-EF5 uptake correlated with baseline hypoxia levels. RT caused significant increases in tumor oxygen concentration and hemoglobin oxygen saturation.
conclusionA hypoxia PET imaging agent can measure changes in tumor hypoxic fraction in response to SN30000. These results suggest the utility of (18)F-EF5 PET for monitoring early response to tumor treatment with SN30000 plus RT in the clinical development of this novel hypoxia-activated prodrug.
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