RADIOLABELED CHX(B)-2E4 IS STABLE IN-VIVO AND IS A SUITABLE IMMUNOCONJUGATE FOR TESTING ALPHA-PARTICLE-EMITTING BISMUTH RADIONUCLIDES IN INTERLEUKIN-2 RECEPTOR TARGETED IMMUNOTHERAPY

A murine model system has been established to assess immunotherapeutic approaches to treating interleukin-2 receptor (IL-2R) expressing mali gnancies. A rat IgG(2c) anti-murine p55 lL-2R monoclonal antibody (2E4 ) was successfully chelate coupled and radiolabelled with either Indiu m-lll or Bismuth-206 while retaining full immunoreactivity. The chelat ing agent used in these studies was p(SCNBZ) CHX(B) DTPA. Indium-111 l abeled 2E4 was used to test the in vivo behavior of the immunoconjugat e and pre-select murine tumor lines based on in vivo radiolabel uptake . The CHX(B)-2E4 MAb was labelled with either Bismuth-206 or iodine-13 1 and the two independently radiolabelled antibodies given simultaneou sly to tumor-bearing nude mice. Both isotopes were found to have equiv alent blood clearance and tissue distributions. In addition, 100 perce nt of the bismuth activity in 1 and 4 hour postinjection serum samples was able to bind to IL-2R expressing cells, while 3 percent bound to an equivalent number of IL-2R negative cells. The time course of in vi vo tumor targeting indicated that 25-35 percent of the i.v. injected d ose per gram tissue (ID/g) was taken up by a subcutaneous IL-2R positi ve murine solid tumor (EL4J3.4) by 24 h post-injection. In contrast, 8 percent (ID/g) was taken up by the IL-2R receptor negative parental t umor (EL4J). Hence, radiolabeled CHX(B)-2E4 is stable in vivo and is a suitable immunoconjugate for testing alpha-emitting bismuth radionucl ides in anti-IL-2R immunotherapy.