Journal article
Targeting CD146 with a Cu-64-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas
Proceedings of the National Academy of Sciences - PNAS, Vol.112(47), pp.E6525-E6534
11/24/2015
DOI: 10.1073/pnas.1502648112
PMCID: PMC4664343
PMID: 26553993
Abstract
Given the highly heterogeneous character of brainmalignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positronemission tomography (PET) imaging of orthotopic GBM models. 64Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (similar to 2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (chi(2) = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.
Details
- Title: Subtitle
- Targeting CD146 with a Cu-64-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas
- Creators
- Yunan Yang - University of Wisconsin–MadisonReinier Hernandez - University of Wisconsin–MadisonJun Rao - Army Medical UniversityLi Yin - Southwest HospitalYazhuo Qu - Southwest HospitalJinrong Wu - Southwest HospitalChristopher G. England - University of Wisconsin–MadisonStephen A. Graves - University of Wisconsin–MadisonChristina M. Lewis - University of Wisconsin–MadisonPu Wang - Southwest HospitalMary E. Meyerand - University of Wisconsin–MadisonRobert J. Nickles - University of Wisconsin–MadisonXiu-wu Bian - Southwest HospitalWeibo Cai - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.112(47), pp.E6525-E6534
- Publisher
- Natl Acad Sciences
- DOI
- 10.1073/pnas.1502648112
- PMID
- 26553993
- PMCID
- PMC4664343
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Number of pages
- 10
- Grant note
- T32GM008349 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) DGE-1256259 / National Science Foundation; National Science Foundation (NSF) 1R01CA169365; P30CA014520; T32CA009206; 5T32GM08349 / National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering, National Cancer Institute University of Wisconsin-Madison W81XWH-11-1-0644; W81XWH-11-1-0648 / Department of Defense; United States Department of Defense R01CA169365; P30CA014520; T32CA009206 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 125246-RSG-13-099-01-CCE / American Cancer Society H1808-81201140 / Chinese Academy of Sciences
- Language
- English
- Date published
- 11/24/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383917602771
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