The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy
The response of radiation-induced fibrosarcoma1 (RIF-1) tumors treated with the vascular-disrupting agent (VDA) ZD6126 was assessed by in vivo and ex vivo1H magnetic resonance spectroscopy (MRS) methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho) in v...
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| Format: | Article |
| Language: | English |
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Elsevier
2006-07-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558606800114 |
| _version_ | 1811321960279310336 |
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| author | Basetti Madhu John C. Waterton John R. Griffiths Anderson J. Ryan Simon P. Robinson |
| author_facet | Basetti Madhu John C. Waterton John R. Griffiths Anderson J. Ryan Simon P. Robinson |
| author_sort | Basetti Madhu |
| collection | DOAJ |
| description | The response of radiation-induced fibrosarcoma1 (RIF-1) tumors treated with the vascular-disrupting agent (VDA) ZD6126 was assessed by in vivo and ex vivo1H magnetic resonance spectroscopy (MRS) methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho) in vivo 24 hours after treatment, whereas control tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed tumor tissues and tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS) and 1H MRS of metabolite extracts revealed a significant reduction in phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated tumors, confirming in vivo tCho response. ZD6126-induced reduction in choline compounds is consistent with a reduction in cell membrane turnover associated with necrosis and cell death following disruption of the tumor vasculature. In vivo tumor tissue water diffusion and lactate measurements showed no significant changes in response to ZD6126. Spin-spin relaxation times (T2) of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential biomarker of tumor response to VDAs in RIF-1 tumors. |
| first_indexed | 2024-04-13T13:25:46Z |
| format | Article |
| id | doaj.art-162bfad616e74b7ea12eac58c65bf1b5 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T13:25:46Z |
| publishDate | 2006-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-162bfad616e74b7ea12eac58c65bf1b52022-12-22T02:45:07ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022006-07-018756056710.1593/neo.06319The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance SpectroscopyBasetti Madhu0John C. Waterton1John R. Griffiths2Anderson J. Ryan3Simon P. Robinson4Cancer Research UK Biomedical Magnetic Resonance Research Group, St. George's, University of London, London SW17 ORE, UKDepartments of Imaging, Global Sciences, Information, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UKCancer Research UK Biomedical Magnetic Resonance Research Group, St. George's, University of London, London SW17 ORE, UKCancer and Infection Research, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UKCancer Research UK Biomedical Magnetic Resonance Research Group, St. George's, University of London, London SW17 ORE, UKThe response of radiation-induced fibrosarcoma1 (RIF-1) tumors treated with the vascular-disrupting agent (VDA) ZD6126 was assessed by in vivo and ex vivo1H magnetic resonance spectroscopy (MRS) methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho) in vivo 24 hours after treatment, whereas control tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed tumor tissues and tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS) and 1H MRS of metabolite extracts revealed a significant reduction in phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated tumors, confirming in vivo tCho response. ZD6126-induced reduction in choline compounds is consistent with a reduction in cell membrane turnover associated with necrosis and cell death following disruption of the tumor vasculature. In vivo tumor tissue water diffusion and lactate measurements showed no significant changes in response to ZD6126. Spin-spin relaxation times (T2) of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential biomarker of tumor response to VDAs in RIF-1 tumors.http://www.sciencedirect.com/science/article/pii/S1476558606800114ZD6126vascular disruptioncholine1H MRSHRMAS |
| spellingShingle | Basetti Madhu John C. Waterton John R. Griffiths Anderson J. Ryan Simon P. Robinson The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy Neoplasia: An International Journal for Oncology Research ZD6126 vascular disruption choline 1H MRS HRMAS |
| title | The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy |
| title_full | The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy |
| title_fullStr | The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy |
| title_full_unstemmed | The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy |
| title_short | The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy |
| title_sort | response of rif 1 fibrosarcomas to the vascular disrupting agent zd6126 assessed by in vivo and ex vivo1h magnetic resonance spectroscopy |
| topic | ZD6126 vascular disruption choline 1H MRS HRMAS |
| url | http://www.sciencedirect.com/science/article/pii/S1476558606800114 |
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