The potential of hyperpolarized (13)C magnetic resonance spectroscopy to monitor the effect of combretastatin based vascular disrupting agents
| Autor: | Hans Stødkilde-Jørgensen, Ane B. Iversen, Morten Busk, Johan Bussink, Lotte Bonde Bertelsen, Michael R. Horsman, Thomas Nielsen, Jasper Lok, Christoffer Laustsen, Thomas Wittenborn, Ole Lajord Munk |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Mammary Neoplasms Tumor vasculature Neovascularization 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Journal Article Radiology Nuclear Medicine and imaging Tissue distribution Combretastatin business.industry Tumor shrinkage Hematology General Medicine Nuclear magnetic resonance spectroscopy 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Cancer research medicine.symptom Nuclear medicine business Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] |
| Zdroj: | Acta Oncologica, 56, 11, pp. 1626-1633 Iversen, A B, Busk, M, Bertelsen, L B, Laustsen, C, Munk, O L, Nielsen, T, Wittenborn, T R, Bussink, J, Lok, J, Stødkilde-Jørgensen, H & Horsman, M R 2017, ' The potential of hyperpolarized (13)C magnetic resonance spectroscopy to monitor the effect of combretastatin based vascular disrupting agents ', Acta Oncologica, vol. 56, pp. 1-8 . https://doi.org/10.1080/0284186X.2017.1351622 Acta Oncologica, 56, 1626-1633 |
| ISSN: | 0284-186X |
| Popis: | Contains fulltext : 181814.pdf (Publisher’s version ) (Closed access) BACKGROUND: Targeting tumor vasculature with vascular disrupting agents (VDAs) results in substantial cell death that precede tumor shrinkage. Here, we investigate the potential of hyperpolarized magnetic resonance spectroscopy (HPMRS) to monitor early metabolic changes associated with VDA treatment. METHODS: Mice bearing C3H mammary carcinomas were treated with the VDAs combretastatin-A4-phosphate (CA4P) or the analog OXi4503, and HPMRS was performed following [1-(13)C]pyruvate administration. Similarly, treated mice were positron emission tomography (PET) scanned following administration of the glucose analog FDG. Finally, metabolic imaging parameters were compared to tumor regrowth delay and measures of vascular damage, derived from dynamic contrast-agent enhanced magnetic resonance imaging (DCE-MRI) and histology. RESULTS: VDA-treatment impaired tumor perfusion (histology and DCE-MRI), reduced FDG uptake, increased necrosis, and slowed tumor growth. HPMRS, revealed that the [1-(13)C]pyruvate-to-[1-(13)C]lactate conversion remained unaltered, whereas [1-(13)C]lactate-to-[(13)C]bicarbonate (originating from respiratory CO2) ratios increased significantly following treatment. CONCLUSIONS: DCE-MRI and FDG-PET revealed loss of vessel functionality, impaired glucose delivery and reduced metabolic activity prior to cell death. [1-(13)C]lactate-to-[(13)C]bicarbonate ratios increased significantly during treatment, indicating a decline in respiratory activity driven by the onset of hypoxia. HPMRS is promising for early detection of metabolic stress inflicted by VDAs, which cannot easily be inferred based on blood flow measurements. |
| Databáze: | OpenAIRE |
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