Molecular MRI enables early and sensitive detection of brain metastases.
Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MR...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2012
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| _version_ | 1826298795738005504 |
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| author | Serres, S Soto, MS Hamilton, A McAteer, M Carbonell, W Robson, M Ansorge, O Khrapitchev, A Bristow, C Balathasan, L Weissensteiner, T Anthony, D Choudhury, R Muschel, R Sibson, N |
| author_facet | Serres, S Soto, MS Hamilton, A McAteer, M Carbonell, W Robson, M Ansorge, O Khrapitchev, A Bristow, C Balathasan, L Weissensteiner, T Anthony, D Choudhury, R Muschel, R Sibson, N |
| author_sort | Serres, S |
| collection | OXFORD |
| description | Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1-targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1-targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3-3 × 10(5) cells) than those volumes detectable clinically (10(7)-10(8) cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients. |
| first_indexed | 2024-03-07T04:52:16Z |
| format | Journal article |
| id | oxford-uuid:d5614cca-57ab-4a7a-b8c9-092f2419949f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:52:16Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:d5614cca-57ab-4a7a-b8c9-092f2419949f2022-03-27T08:25:36ZMolecular MRI enables early and sensitive detection of brain metastases.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d5614cca-57ab-4a7a-b8c9-092f2419949fEnglishSymplectic Elements at OxfordNational Academy of Sciences2012Serres, SSoto, MSHamilton, AMcAteer, MCarbonell, WRobson, MAnsorge, OKhrapitchev, ABristow, CBalathasan, LWeissensteiner, TAnthony, DChoudhury, RMuschel, RSibson, NMetastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1-targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1-targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3-3 × 10(5) cells) than those volumes detectable clinically (10(7)-10(8) cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients. |
| spellingShingle | Serres, S Soto, MS Hamilton, A McAteer, M Carbonell, W Robson, M Ansorge, O Khrapitchev, A Bristow, C Balathasan, L Weissensteiner, T Anthony, D Choudhury, R Muschel, R Sibson, N Molecular MRI enables early and sensitive detection of brain metastases. |
| title | Molecular MRI enables early and sensitive detection of brain metastases. |
| title_full | Molecular MRI enables early and sensitive detection of brain metastases. |
| title_fullStr | Molecular MRI enables early and sensitive detection of brain metastases. |
| title_full_unstemmed | Molecular MRI enables early and sensitive detection of brain metastases. |
| title_short | Molecular MRI enables early and sensitive detection of brain metastases. |
| title_sort | molecular mri enables early and sensitive detection of brain metastases |
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