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 Google Scholar Google Scholar Articles by Pallela, V. R. Articles by Thakur, M. L. Search for Related Content PubMed PubMed Citation Articles by Pallela, V. R. Articles by Thakur, M. L.

Interferon--2b Immunoconjugate for Improving Immunoscintigraphy and Immunotherapy

Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

Correspondence: For correspondence or reprints contact: Mathew L. Thakur, PhD, Department of Radiology, Thomas Jefferson University Hospital, 1020 Locust St., Ste. 359 JAH, Philadelphia, PA 19107.

ABSTRACT

A pretreatment with a single dose of an immunoconjugate (IC) that promises to enhance tumor uptake and decrease liver uptake of radiolabeled monoclonal antibodies (MAbs) might be of use in radioimmunodetection and radioimmunotherapy (RIT). We have shown previously that an interferon (IFN)-MAb (1:1) immunoconjugate (IC) enhances tumor uptake by a factor of 2 or more and reduces liver uptake by 50% in nude mice bearing human tumors. The aim of this study was to determine whether IFN modulates antigenic expression and to ascertain the most effective route of its administration, the optimal quantity to be administered, and the optimal duration of time to lapse between the administration of IC and the radiolabeled MAb. Methods: IFN--2b and anticarcinoembryonic antigen-F6 (lgG2a) MAb were conjugated (1:1), and F(ab')₂ of the MAb was labeled with ^99mTc. Human colorectal tumors were grown in nude mice by implanting 5 x 10⁶ LS174T confluent cells grown in culture. Mice, 5 in each group, received 20 x 10³ IU intravenously, intramuscularly, or intraperitoneally and 40 x 10³, 60 x 10³, and 80 x 10³ IU intravenously 30 min before the intravenous administration of 25.9 MBq ^99mTc/20 µg F(ab')₂. Mice in the control groups received ^99mTc-F(ab')₂ but not the conjugate. Twenty-four hours later mice were killed and imaged, and tissues were removed for quantitative (percentage injected dose/g [% ID/g]) distribution of ^99mTc. Results: In all conjugate-receiving mice, the tumor uptake was higher and the liver uptake was lower (P < 0.01) than that in the control mice with the exception of liver uptake, which was not significantly different in mice receiving 80 x 10³ IU conjugate. The optimal results were apparent in mice pretreated with 40 x 10³ IU conjugate in which tumor uptake was enhanced by a factor of 2.3 (4.8 ± 0.5 %ID/g versus 11 ± 0.7 %ID/g; P < 0.01). The renal uptake remained unchanged, and the tumor-to-muscle ratios increased from 11.5 ± 6.8 to 14.6 ± 3.9, and the tumor-to-blood ratios increased from 4.4 ± 1.8 to 8.3 ± 2.4. The liver uptake decreased from 9.5% ± 1% to 5% ± 1.6%. Results were attributed to enhanced tumor blood flow, increased antigenic expression, and blocking of hepatic nonspecific Fc receptors. Conclusion:A pretreatment with IFN-MAb conjugate is a worthwhile approach to consider in radioimmunoscintigraphy and RIT.

Key Words: immoconjugate • interferon-monoclonal antibody conjugate • improving RIS and RIT