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CD30 is a member of the TNF receptor superfamily. Overexpression of CD30 on some neoplasms versus limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. In this study, we evaluated the therapeutic efficacy of an anti-CD30 antibody, HeFi-1, armed with [sup.211]At in a leukemia (karpas299) model and with [sup.90]Y in a lymphoma (SUDHL-1) model. Furthermore, we investigated the combination therapy of [sup.211]At-HeFi-1 with unmodified HeFi-1 in the leukemia model, Treatment with unmodified HeFi-1 significantly prolonged the survival of the karpas299-bearing mice compared with the controls (P < 0.001). Treatment with [sup.211]At-HeFi-1 showed greater therapeutic efficacy than that with unmodified HeFi-1 as shown by survival of the mice (P < 0.001). Combining these two agents further improved the survival of the mice compared with the groups treated with either [sup.211]At-HeFi-1 (P < 0.05) or unmodified HeFi-1 (P < 0.001) alone. In the lymphoma model, the survival of the SUDHL-1-bearing mice was significantly prolonged by the treatment with [sup.90]Y-HeFi-1 compared with the controls (P < 0.001). In summary, radiolabeled HeFi-1 is very promising for the treatment of CD30-expressing leukemias and lymphomas, and the combination regimen of [sup.211]At-HeFi-1 with unmodified HeFi-1 enhanced the therapeutic efficacy. monoclonal antibody | radioimmunotherapy | s-emitter | [beta]-emitter

Although radioimmunotherapy with radiolabeled intact monoclonal antibodies has demonstrated efficacy in the treatment of lymphoma, it provides low tumor-to-normal-tissue radionuclide target ratios and unwanted prolonged radiation exposure to the bone marrow. To overcome these obstacles, the administration of the radionuclide was separated from that of the antibody by using an anti-IL-2 receptor [alpha] antibody single chain Fv-streptavidin fusion protein, followed by radiolabeled biotin to treat lymphoma or leukemia xenografted mice. This Pretarget approach provided extremely rapid and effective tumor targeting, permitting the use of short-lived [alpha]-emitting radionuclides. With the [beta]-emitter [sup.90]Y, all of the 10 lymphoma-xenografted mice were cured. With the [alpha]-emitter [sup.213]Bi, significant efficacy was obtained in treating leukemic mice, and, furthermore, when combined with immunotherapy, 7 of 10 leukemic mice were cured. Thus, Pretarget radio-immunotherapy is very promising and could represent the next generation in the treatment of lymphoma and leukemia.

Research has been conducted on the diethylenetriaminepentaacetic acid derivatives. The synthesis of these derivatives as the contrast enhancement agents in MRI has been carried out and the results indicate the presence of the T1 and T2 relaxivities in the corresponding gadolinium(III) complexes.