The non-Hodgkin's lymphomas represent a clinically most significant model for tumor localization studies. The important contribution of initial disease localization to the successful treatment of patients with non- Hodgkin's lymphomas is well established. The objective of this proposal is well established. The objective of this proposal is to assess the in vivo diagnostic potential of two monoclonal antibodies (BA-1 and BA-3) that show reactivity against B-cell lymphomas. The majority (80%) of non- Hodgkin's lymphomas in adults are malignancies of B-lymphocytes. A feature of lymphomas is that they have a high blood flow.
The specific aims are: (1) to develop methods of producing 131-I, 123-I and 111-In-labeled BA-1 or BA-3 antibody preparations, (2) to assess th tumor localization of radiolabeled BA-1 or BA-3 antibodies in vitro and in vivo human B- lumphocyte experimental tumor systems, and (3) to assess the safety and utility of radiolabeled BA-1 or BA-3 antibody proparations for the in vivo localization of B-cell lymphomas in adults with non-Hodgkin's lymphoma. The tumor localization and biodistributyion of the radio- labeled antibody preparations will be studied in nude mice bearing subcutaneous transplants of human B-cell lymphoma lines using tissue sampling and external scintigraphy. The parameters to be investigated are the antibody, radiolabel, dose, time after administration, the use of whole antibody or antibody fragments, and tumor size. Side effects of antibody administration will be monitored in patients to ensure the safety of continued testing. The optimal dose of radiolabeled antibody, time of imaging and technique of imaging will be evaluated. The sensitivity and specificity of the imaging technique will be determined in general, and in the face of specific variables that include anatomic sites, tumor size and bulk. Initially, radioimmunologic imaging will be performed only in patients with a recurrence of their lymphoma following prior therapy. In patients with advanced previously treated lymphoma that have positive sites of anitbody localization and response subsequent to therapy, additional localization studies will be performed at the time of best remission and at the time of subsequent relapse. The technique, if promising will also be evaluated in newly diagnosed and untreated pateints. The plan is to enter 10-15 patients with recurrent lymphoma initially. Subsequently, 10-15 advanced B-cell lymphoma patients with various sites of recurrent disease or with defined metastatic lesions will be studied.
