title: Visualization of Connexin 43-positive cells of glioma and the periglioma zone by means of intravenously injected monoclonal antibodies.
abstract: The selectivity of monoclonal antibodies against the E2 extracellular fragment of connexin 43 (Cx43) for a glioma focus was studied in in vivo experiments on animals with intracranial C6 glioma. Antibodies labeled with two alternative labels, the radioisotope (125)I and the fluorophore Alexa 660, were intravenously injected to rats with 18-day gliomas. Seventy-two hours after injection, (125)I-labeled antibodies accumulated in the hemisphere where the glioma was located to a concentration of 0.27 ± 0.01% of the injected dose per gram of wet weight, which exceeded their accumulation in the liver, spleen, and other organs. Fluorescent-labeled antibodies against the Cx43 fragment E2 specifically visualized cells in the peritumoral astroglial bank (a zone of active invasion of glioma cells). Double immunofluorescent visualization using antibodies against the Cx43 fragment E2 and glial fibrillar acidic protein (GFAP) showed that only a small proportion of the cells that bound the antibodies injected into the blood circulation were reactive astrocytes, whereas most of these cells were GFAP-negative and morphologically corresponded to astroblasts. These results suggest that antibodies against the extracellular Cx43 fragment E2 can be used for targeted transport of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas.
authors.affiliation: Pirogov Russian State Medical University, Chair of Medicinal Nanobiotechnology, Moscow, Russia. serpoff@gmail.com
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Baklaushev
authors.forename: Gaukhar M
authors.initials: GM
authors.lastname: Yusubalieva
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Tsitrin
authors.forename: Olga I
authors.initials: OI
authors.lastname: Gurina
authors.forename: Nadezhda Ph
authors.initials: NP
authors.lastname: Grinenko
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Victorov
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Chekhonin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001253:Astrocytes / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000000981:diagnostic imaging*; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein; D007457:Iodine Radioisotopes