HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kobayashi, H. Articles by Konishi, J. Search for Related Content PubMed PubMed Citation Articles by Kobayashi, H. Articles by Konishi, J.

Improved Clearance of Radiolabeled Biotinylated Monoclonal Antibody Following the Infusion of Avidin as a "Chase" without Decreased Accumulation in the Target Tumor

Departments of Radiology and Nuclear Medicine, Faculty of Medicine, Institute for Virus Research, Kyoto University, Kyoto
Department of Nuclear Medicine, Gunma University, School of Medicine, Maebashi, Japan

Correspondence: For correspondence or reprints contact: Hisataka Kobayashi, MD, Dept. of Radiology and Nuclear Medicine, Kyoto University, Faculty of Medicine, 54, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-01, Japan.

ABSTRACT

The techniques of radioimmunoimaging and radioimmunotherapy suffer from prolonged high background radioactivity because intravenously injected antibodies remain in the circulation and in the organs far longer than necessary for effective binding to the target. To decrease background and increase radionuclide excretion without decreasing the dose of radioactivity delivered to the target tumor, we used radiolabeled biotinylated antibodies followed by a "chase" avidin injection. Methods: A mouse monoclonal antibody, OST7 (IgG1), which reacts with human osteosarcoma, was biotinylated and labeled with ¹²⁵I, ¹³¹I or ^99mTc. Radiolabeled biotinylated OST7 (10 µg) was administered intravenously into nude mice bearing human osteosarcomas and 30 µg of avidin was injected intravenously 6 or 24 hr later. Results: Following avidin injection in mice pretreated with radiolabeled biotinylated antibodies, radioactivity was promptly cleared from the blood and deposited in the liver and spleen, after which radioiodine was rapidly detached from the antibody and excreted in the urine. The tumor-to-blood ratios at 6 and 24 hr after the injection of ¹²⁵I-labeled biotinylated OST7 increased compared with the values before the avidin chase without any loss of tumor radioactivity. Furthermore, the tumor-to-background radioactivity ratio was improved and better images were obtained more rapidly after the injection of radiolabeled biotinylated antibodies than with conventional immunoscintigraphy. Conclusions: This method may find application in clinical radioimmunoimaging, especially using short half-life radionuclides such as ^99mTc and ¹²³I.

Key Words: monoclonal antibody • avidin • biotin • chase • immunoscintigraphy

This article has been cited by other articles:

				V. Tolmachev, A. Orlova, R. Pehrson, J. Galli, B. Baastrup, K. Andersson, M. Sandstrom, D. Rosik, J. Carlsson, H. Lundqvist, et al. Radionuclide Therapy of HER2-Positive Microxenografts Using a 177Lu-Labeled HER2-Specific Affibody Molecule Cancer Res., March 15, 2007; 67(6): 2773 - 2782. [Abstract] [Full Text] [PDF]

				Y. Hama, Y. Urano, Y. Koyama, M. Kamiya, M. Bernardo, R. S. Paik, I. S. Shin, C. H. Paik, P. L. Choyke, and H. Kobayashi A Target Cell-Specific Activatable Fluorescence Probe for In vivo Molecular Imaging of Cancer Based on a Self-Quenched Avidin-Rhodamine Conjugate Cancer Res., March 15, 2007; 67(6): 2791 - 2799. [Abstract] [Full Text] [PDF]

				M. Mamede, T. Saga, H. Kobayashi, T. Ishimori, T. Higashi, N. Sato, M. W. Brechbiel, and J. Konishi Radiolabeling of Avidin with Very High Specific Activity for Internal Radiation Therapy of Intraperitoneally Disseminated Tumors Clin. Cancer Res., September 1, 2003; 9(10): 3756 - 3762. [Abstract] [Full Text] [PDF]

				H. Kobayashi, K. Shirakawa, S. Kawamoto, T. Saga, N. Sato, A. Hiraga, I. Watanabe, Y. Heike, K. Togashi, J. Konishi, et al. Rapid Accumulation and Internalization of Radiolabeled Herceptin in an Inflammatory Breast Cancer Xenograft with Vasculogenic Mimicry Predicted by the Contrast-enhanced Dynamic MRI with the Macromolecular Contrast Agent G6-(1B4M-Gd)256 Cancer Res., February 1, 2002; 62(3): 860 - 866. [Abstract] [Full Text] [PDF]