title: Injection site radioactivity of (99m)Tc-labeled mannosylated dextran for sentinel lymph node mapping.
abstract: The high and persistent radioactivity at the injection site hinders the accuracy and expansion of sentinel lymph node (SLN) mapping. We investigated the mechanism underlying the undesirable radioactivity after subcutaneous injection of (99m)Tc-labeled mannosylated dextran ((99m)Tc(CO)3-DCM20), a SLN mapping agent targeting mannose receptors on macrophages and dendritic cells, in a mouse model. Biodistribution studies were performed 1 h after subcutaneous injection of (99m)Tc(CO)3-DCM20 from the rear footpad of mice in the presence of varying molar amounts of DCM20 or DC15, a modified dextran without mannose. Biodistribution studies were also conducted after subcutaneous injection of [(125)I]radioiodinated mannosyl-neoglycoalbumin ((125)I-NMA) from the rear footpad. The distribution of fluorescence-labeled DCM20 and DC15 at the injection site was also compared 1 h after subcutaneous injection by immunofluorescent histochemistry. The radioactivity levels of (99m)Tc(CO)3-DCM20 at the injection site and popliteal lymph node, a SLN in this model, decreased with an increase in the molar amounts of DCM20, whereas no significant changes in biodistribution were observed after injection of (99m)Tc(CO)3-DCM20 with varying molar amounts of DC15. (125)I-NMA exhibited rapid elimination of radioactivity from both the popliteal lymph node and the injection site. The fluorescence-labeled DCM20 colocalized well with CD68-positive cells such as macrophages and dendritic cells at the injection site. While partial colocalization was observed between DC15 and CD68-positive cells, the signal intensity was very weak. These findings suggest that specific binding of (99m)Tc(CO)3-DCM20 to the mannose receptor on macrophages and dendritic cells would be responsible for the sustained radioactivity levels at the injection site. These results also imply that discriminated blockage of (99m)Tc(CO)3-DCM20 binding to mannose receptors at the injection sites would reduce the radioactivity at the injection site.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Ioannis
authors.initials: I
authors.lastname: Pirmettis
authors.forename: Tomoya
authors.initials: T
authors.lastname: Uehara
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tsushima
authors.forename: Minas
authors.initials: M
authors.lastname: Papadopoulos
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D037181:Lectins, C-Type / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D015609:Organotechnetium Compounds / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*
chemical_list: D003911:Dextrans; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D015609:Organotechnetium Compounds; D011956:Receptors, Cell Surface
keywords: dendritic cell; injection site; macrophage; mannose receptor; mannosylated dextran; sentinel lymph node