These studies are designed to develop improved methods for detecting and treating malignancies. Our group performs preclinical evaluation of antibodies that appear to be promising after initial screening by various laboratories at the National Cancer Institute and develops these antibodies for clinical staff. They are then administered to patients under the supervision of a nuclear medicine physician and an assistant in the Nuclear Medicine Department. Serial blood samples, urine specimens, and often bone marrow or tumor biopsies are obtained to evaluate the distribution of the monoclonal antibody in the body. The phase I trial with B3, in collaboration with Dr. Ira Pastan, is continuing patient accrual. We have accrued 20 patients and are at our fourth dose level. Based on the preliminary results of our collaborative radioimmunotherapy trial with Dr. Waldmann in which we used humanized anti-tac monoclonal antibody, we have designed another trial using Ca-DTPA to sequester any free Y-90 that comes from the antibody. The DTPA is expected to chelate free Y-90 on this to minimize the concentration of Y-90 in the bone marrow, which should will allow higher doses of Y-90 anti-Tac to be administered. We have labeled anti-tac dsFv monoclonal antibody fragment with various radioisotopes and evaluated their biodistribution in nude mice with tumor xenografts. This study demonstrated rapid and specific targeting of tumors. The major limitation was the high concentration of tracer found in the kidneys. In a subsequent study, we demonstrated that by using lysine or other amino acid solutions we could block the high renal uptake effectively. When using tumor xenografts of SP2/Tac, a cell line that expresses the interleukin-2R (IL-2R) receptor, we found evidence of in vivo complex formation that resulted in altered kinetics of the radiolabeled dsFv. We then demonstrated that we could block the circulating IL-2Ro by preinjecting the mice with humanized anti-tac immunoglobulin G (IgG). Because of its large size, the humanized IgG blocked the circulating IL-2Ro but did not adversely affect tumor binding of (did not compete with) the dsFv because the dsFv rapidly cleared from the circulation and targeted tumor.