Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model

Joseph F. Georges, Xiaowei Liu, Jennifer Eschbacher, Joshua Nichols, Michael A. Mooney, Anna Joy, Robert F. Spetzler, Burt G. Feuerstein, Mark C. Preul, Trent Anderson, Hao Yan, Peter Nakaji

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9 Citations (Scopus)

Abstract

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

Original languageEnglish
Article numbere0123607
JournalPloS one
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 15 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Georges, J. F., Liu, X., Eschbacher, J., Nichols, J., Mooney, M. A., Joy, A., Spetzler, R. F., Feuerstein, B. G., Preul, M. C., Anderson, T., Yan, H., & Nakaji, P. (2015). Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model. PloS one, 10(4), [e0123607]. https://doi.org/10.1371/journal.pone.0123607