Interferon-alpha-2b immunoconjugate for improving immunoscintigraphy and immunotherapy

A pretreatment with a single dose of an immunoconjugate (IC) that promises to enhance tumor uptake and decrease liver uptake of radiolabeled monoclona l antibodies (MAbs) might be of use in radioimmunodetection and radioimmuno therapy (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 red uces river uptake by 50% in nude mice bearing human tumors. The aim of this study was to determine whether IFN modulates antigenic expression and to a scertain the most effective route of its administration, the optimal quanti ty to be administered, and the optimal duration of time to lapse between th e administration of IC and the radiolabeled MAb. Methods: IFN-alpha-2b and anticarcinoembryonic antigen-F6 (IgG2a) MAb were conjugated (1:1), and F(ab ')(2) of the MAb was labeled with (TC)-T-99m. Human colorectal tumors were grown in nude mice by implanting 5 x 10(6) LS174T confluent cells grown in culture. Mice, 5 in each group, received 20 x 10(3) IU intravenously, intra muscularly, or intraperitoneally and 40 x 10(3), 60 x 10(3), and 80 x 10(3) IU intravenously 30 min before the intravenous administration of 25.9 MBq (TC)-T-99m/20 mu g F(ab')(2). Mice in the control groups received Tc-99m-F( ab')(2) but not the conjugate. Twenty-four hours later mice were killed and imaged, and tissues were removed for quantitative (percentage injected dos e/g [% [D/g]) distribution of (TC)-T-99m. Results: in all conjugate-receivi ng mice, the tumor uptake was higher and the liver uptake was tower (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 10(3) IU conjugate. The optimal results were apparent in mice pretreated with 40 x 10(3) IU co njugate 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 unchang ed, 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, a nd blocking of hepatic nonspecific Fc receptors. Conclusion: A pretreatment with IFN-MAb conjugate is a worthwhile approach to consider in radioimmuno scintigraphy and RIT.