Molecular MRI enables early and sensitive detection of brain metastases

作者：Serres Sebastien; Soto Manuel Sarmiento; Hamilton Alastair; McAteer Martina A; Carbonell W Shawn; Robson Matthew D; Ansorge Olaf; Khrapitchev Alexandre; Bristow Claire; Balathasan Lukxmi; Weissensteiner Thomas; Anthony Daniel C; Choudhury Robin P; Muschel Ruth J; Sibson Nicola R^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(17): 6674-6679.

DOI：10.1073/pnas.1117412109

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 x 105 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.

• 出版日期2012-4-24