ArticleProceedings of the National Academy of Sciences of the United States of America2011
Preclinical evaluation and validation of [18F]HX4, a promising hypoxia marker for PET imaging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Limitations of Fluorine 18 Fluoromisonidazole in Assessing Treatment-induced Tissue Hypoxia after Transcatheter Arterial Embolization of Hepatocellular Carcinoma: A Prospective Pilot Study.Radiology. Imaging cancer · 2022Trial
- Evaluation of tumour hypoxia during radiotherapy using [European journal of nuclear medicine and molecular imaging · 2016Trial
- Repeatability of hypoxia PET imaging using [¹⁸F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial.European journal of nuclear medicine and molecular imaging · 2015Trial
- Hypoxia Imaging in Lung Cancer: A PET-Based Narrative Review for Clinicians and Researchers.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Optimising hypoxia PET imaging and its applications in guiding targeted radiation therapy for non-small cell lung cancer: a scoping review.Journal of medical radiation sciences · 2025Article
- Article
- High-LET charged particles: radiobiology and application for new approaches in radiotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- Functional Imaging of Hypoxia: PET and MRI.Cancers · 2023Review
- Predicting the Tumour Response to Radiation by Modelling the Five Rs of Radiotherapy Using PET Images.Journal of imaging · 2023Article
- Advances in PET and MRI imaging of tumor hypoxia.Frontiers in medicine · 2023Review
- Hypoxia Imaging As a Guide for Hypoxia-Modulated and Hypoxia-Activated Therapy.Antioxidants & redox signaling · 2022Review
- Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose.Frontiers in medicine · 2022Review
- The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia.Frontiers in pharmacology · 2022Review
- Molecular Imaging of Vulnerable Coronary Plaque with Radiolabeled Somatostatin Receptors (SSTR).Journal of clinical medicine · 2021Review
- Imaging carbonic anhydrase IX as a method for monitoring hypoxia-related radioresistance in preclinical head and neck cancer models.Physics and imaging in radiation oncology · 2021Article
- Identification of proteins and cellular pathways targeted by 2-nitroimidazole hypoxic cytotoxins.Redox biology · 2021Article
- Hypoxia and the phenomenon of immune exclusion.Journal of translational medicine · 2021Review
- Imaging of Tumor Hypoxia With Radionuclide-Labeled Tracers for PET.Frontiers in oncology · 2021Review
- Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy.Frontiers in oncology · 2021Review
- Soluble Compounds Released by Hypoxic Stroma Confer Invasive Properties to Pancreatic Ductal Adenocarcinoma.Biomedicines · 2020Article
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12 authors.
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Abstract
Hypoxia has been shown to be an important microenvironmental parameter influencing tumor progression and treatment efficacy. Patient guidance for hypoxia-targeted therapy requires evaluation of tumor oxygenation, preferably in a noninvasive manner. The aim of this study was to evaluate and validate the uptake of [(18)F]HX4, a novel developed hypoxia marker for PET imaging. A heterogeneous accumulation of [(18)F]HX4 was found within rat rhabdomyosarcoma tumors that was significantly (P < 0.0001) higher compared with the surrounding tissues, with temporal increasing tumor-to-blood ratios reaching a plateau of 7.638 ± 0.926 and optimal imaging properties 4 h after injection. [(18)F]HX4 retention in normal tissues was found to be short-lived, homogeneous and characterized by a fast progressive temporal clearance. Heterogeneity in [(18)F]HX4 tumor uptake was analyzed based on 16 regions within the tumor according to the different orthogonal planes at the largest diameter. Validation of heterogeneous [(18)F]HX4 tumor uptake was shown by a strong and significant relationship (r = 0.722; P < 0.0001) with the hypoxic fraction as calculated by the percentage pimonidazole-positive pixels. Furthermore, a causal relationship with tumor oxygenation was established, because combination treatment of nicotinamide and carbogen resulted in a 40% reduction (P < 0.001) in [(18)F]HX4 tumor accumulation whereas treatment with 7% oxygen breathing resulted in a 30% increased uptake (P < 0.05). [(18)F]HX4 is therefore a promising candidate for noninvasive detection and evaluation of tumor hypoxia at a macroscopic level.
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