title: Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.
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.
authors: Division of Neuroscience, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors: Joseph F
authors: JF
authors: Georges
authors: The Biodesign Institute, Arizona State University, Tempe, Arizona.
authors: Xiaowei
authors: X
authors: Liu
authors: Division of Neuropathology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors: Jennifer
authors: J
authors: Eschbacher
authors: College of Medicine, University of Arizona, Phoenix, Arizona.
authors: Joshua
authors: J
authors: Nichols
authors: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors: Michael A
authors: MA
authors: Mooney
authors: Division of Neuroscience, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors: Anna
authors: A
authors: Joy
authors: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors: Robert F
authors: RF
authors: Spetzler
authors: College of Medicine, University of Arizona, Phoenix, Arizona.
authors: Burt G
authors: BG
authors: Feuerstein
authors: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors: Mark C
authors: MC
authors: Preul
authors: College of Medicine, University of Arizona, Phoenix, Arizona.
authors: Trent
authors: T
authors: Anderson
authors: The Biodesign Institute, Arizona State University, Tempe, Arizona.
authors: Hao
authors: H
authors: Yan
authors: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors: Peter
authors: P
authors: Nakaji
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001254:Astrocytoma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D005470:Fluorometry; D006801:Humans; D007432:Intraoperative Period; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D018613:Microscopy, Confocal; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009690:Nucleic Acid Conformation; D011923:Rats, Nude; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous; D000097573:Red Fluorescent Protein
chemical_list: D052157:Aptamers, Nucleotide; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein