title: Sickle red blood cells accumulate in tumor.
abstract: The preferential accumulation of sickle blood cells in tumor vasculature is demonstrated noninvasively using MRI and sickle red blood cells loaded with Gd-DTPA and invasively by two other techniques. The distribution of red blood cells in rat brain tumors relative to normal brains were measured using three separate techniques: MRI of Gd-DTPA loaded cells, fluorescent microscopy detection of Oregon Green 488 fluorescence conjugated to a streptavidin-biotin complex that binds to red blood cell surface proteins, and autoradiography using a technetium (99m)Tc-labeling kit. Labeled red cells were infused intravenously in rats with brain tumors. Sickle cells preferentially accumulated in tumor relative to normal brain, with highest concentrations near the tumor / normal tissue boundary, whereas control normal red cells did not preferentially aggregate at the tumor periphery. This demonstrates the potential of sickle red blood cells to accumulate in the abnormal tumor vessel network, and the ability to detect their aggregation noninvasively and at high spatial resolution using MRI. The application of the noninvasive measurement of sickle cells for imaging tumor neovasculature, or as a delivery tool for therapy, requires further study.
authors.affiliation: Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA. sbrown1@hfhs.org
authors.forename: S L
authors.initials: SL
authors.lastname: Brown
authors.forename: J R
authors.initials: JR
authors.lastname: Ewing
authors.forename: T N
authors.initials: TN
authors.lastname: Nagaraja
authors.forename: P S
authors.initials: PS
authors.lastname: Swerdlow
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: J D
authors.initials: JD
authors.lastname: Fenstermacher
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000098:blood supply; D001932:Brain Neoplasms / Q000098:blood supply* / Q000175:diagnosis; D002264:Carboxylic Acids; D045744:Cell Line, Tumor; D003287:Contrast Media; D004912:Erythrocytes; D005456:Fluorescent Dyes; D019786:Gadolinium DTPA; D005910:Glioma / Q000098:blood supply*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013670:Sodium Pertechnetate Tc 99m
chemical_list: D002264:Carboxylic Acids; D003287:Contrast Media; D005456:Fluorescent Dyes; C436864:Oregon Green 488 carboxylic acid; D013670:Sodium Pertechnetate Tc 99m; D019786:Gadolinium DTPA