Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific

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• 作者：Heather L. McConnell ; B.S.^a ; ^{mcconneh@ohsu.edu" class="auth_mail" title="E-mail the corresponding author} ; Daniel L. Schwartz ; B.A.^b ; ^{schwartd@ohsu.edu" class="auth_mail" title="E-mail the corresponding author} ; Brian E. Richardson ; Ph.D.^c ; ^{brian@brianerichardson.com" class="auth_mail" title="E-mail the corresponding author} ; Randall L. Woltjer ; M.D. ; Ph.D.^d ; ^{woltjerr@ohsu.edu" class="auth_mail" title="E-mail the corresponding author} ; Leslie L. Muldoon ; Ph.D.^a ; ^{muldoonl@ohsu.edu" class="auth_mail" title="E-mail the corresponding author} ; Edward A. Neuwelt ; M.D.^a ; ^e ; ^f ; ^{neuwelte@ohsu.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CNS ; central nervous system ; MRI ; magnetic resonance imaging ; USPIO ; ultrasmall superparamagnetic iron oxide ; BBB ; blood&ndash ; brain barrier
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：12
• 期：6
• 页码：1535-1542
• 全文大小：1492 K

文摘

Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo. We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163⁺/CD68⁺ macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic.