title: Targeted sonodynamic therapy of cancer using a photosensitizer conjugated with antibody against carcinoembryonic antigen.
abstract: The goal of this study was to develop a strategy for the selective destruction of cancer cells by ultrasonic irradiation in the presence of an antibody-conjugated photosensitizer. To this end, a photoimmunoconjugate (PIC) was prepared between ATX-70, a photosensitizer of a gallium-porphyrin analogue, and F11-39, a high affinity monoclonal antibody (MAb) against carcinoembryonic antigen (CEA), which is often overexpressed in various carcinoma cells. This conjugate, designated F39/ATX-70, retained immunoreactivity against purified CEA and CEA-expressing cells as determined by enzyme-linked immunosorbent assay, flow cytometry and immunofluorescence microscopic analysis. The cytotoxicity of F39/ATX-70 against CEA-expressing human gastric carcinoma cells in vitro was found to be greater than that of ATX-70 when applied in combination with ultrasound irradiation. When in vivo anti-tumor effects in a mouse xenograft model were assessed, intravenous administration of F39/ATX-70 followed by ultrasonic irradiation produced a marked growth inhibition of tumor compared with irradiation alone or irradiation after administration of ATX-70. These results suggest that the PIC between anti-CEA MAb and ATX-70 may have applications in sonodynamic therapy where destruction of CEA-expressing tumor is required.
authors.affiliation: Department of Biochemistry, Fukuoka University School of Medicine, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Abe
authors.forename: Motomu
authors.initials: M
authors.lastname: Kuroki
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tachibana
authors.forename: Tieli
authors.initials: T
authors.lastname: Li
authors.forename: Aradhana
authors.initials: A
authors.lastname: Awasthi
authors.forename: Aruto
authors.initials: A
authors.lastname: Ueno
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Imakiire
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamada
authors.forename: Asami
authors.initials: A
authors.lastname: Ariyoshi
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D000918:Antibody Specificity; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D018796:Immunoconjugates / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011166:Porphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D017319:Photosensitizing Agents; D011166:Porphyrins; C081908:ATX 70