Journal article
A novel molecular magnetic resonance imaging agent targeting activated leukocyte cell adhesion molecule as demonstrated in mouse brain metastasis models
- Abstract:
- Molecular magnetic resonance imaging (MRI) allows visualization of biological processes at the molecular level. Upregulation of endothelial ALCAM (activated leukocyte cell adhesion molecule) is a key element for leukocyte recruitment in neurological disease. The aim of this study, therefore, was to develop a novel molecular MRI contrast agent, by conjugating anti-ALCAM antibodies to microparticles of iron oxide (MPIO), for detection of endothelial ALCAM expression in vivo. Binding specificity of ALCAM-MPIO was demonstrated in vitro under static and flow conditions. Subsequently, in a proof-of-concept study, mouse models of brain metastasis were induced by intracardial injection of brain-tropic human breast carcinoma, lung adenocarcinoma or melanoma cells to upregulate endothelial ALCAM. At selected time-points, mice were injected intravenously with ALCAM-MPIO, and ALCAM-MPIO induced hypointensities were observed on T2*-weighted images in all three models. Post-gadolinium MRI confirmed an intact blood-brain barrier, indicating endoluminal binding. Correlation between endothelial ALCAM expression and ALCAM-MPIO binding was confirmed histologically. Statistical analysis indicated high sensitivity (80-90%) and specificity (79-83%) for detection of endothelial ALCAM in vivo with ALCAM-MPIO. Given reports of endothelial ALCAM upregulation in numerous neurological diseases, this advance in our ability to image ALCAM in vivo may yield substantial improvements for both diagnosis and targeted therapy.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 1.7MB, Terms of use)
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- Publisher copy:
- 10.1177/0271678x20968943
Authors
- Publisher:
- SAGE Publications
- Journal:
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism More from this journal
- Volume:
- 41
- Issue:
- 7
- Pages:
- 1592-1607
- Place of publication:
- United States
- Publication date:
- 2020-11-05
- Acceptance date:
- 2020-09-18
- DOI:
- EISSN:
-
1559-7016
- ISSN:
-
0271-678X
- Pmid:
-
33153376
- Language:
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English
- Keywords:
- Pubs id:
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1140976
- Local pid:
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pubs:1140976
- Deposit date:
-
2020-11-23
Terms of use
- Copyright holder:
- Zarghami et al.
- Copyright date:
- 2020
- Rights statement:
- © The Author(s) 2020. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
- Licence:
- CC Attribution (CC BY)
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