Radioimmunodetection of gliomas by administration of radiolabelled monoclonal antibodies. Experimental data
Stavrou, D.; Mellert, W.; Bilzer, T.; Senekowitsch, R.; Keiditsch, E.; Mehraein, P.
Anticancer Research 5(2): 147-156
1985
ISSN/ISBN: 0250-7005 PMID: 3994308 Document Number: 266314
Radiolabeled monoclonal antibodies (McAbs) raised against membrane components of an experimental rat glioma (79FR-G-41) were administered parenterally to immunodeficient mice bearing glioma grafts for tumor radioimmunodetection by external imaging. Purified McAbs (14AC1) of IgG2a isotype were labeled with Na131I (2mCi/50ml) using the Chloramin-T method. As control, for non-specific uptake of proteins in the tumor, normal mouse IgG were also iodinated. For radioimaging, nude mice bearing gliomas in the thigh muscle were injected i.v. with 15 .mu.g of the 131I-McAb with an activity of approximately 150 .mu.Ci. Control tumor-bearing animals received the same amount of mouse 131I-IgG. Scans obtained immediately after injecting the intact 131I-14AC1 antibody and at 24, 48, 72 and 96 h demonstrated accumulation in the tumor. The tumor was clearly visible 48 h following injection of 131I-labeled antibody. At 96 h after injection, the McAb showed a clearly higher uptake into the tumor as the control IgG. The biodistribution of the injected antibody was studied at 96 h after injection following the last .gamma.-imaging. At this time blood activity was still high, but the maximum activity was found in the tumor for the specific McAb. Using the 131I-14AC1 to image glioma transplants, it could be shown that grafts are permeable for the McAb. The time-course experiments administering 131I-14AC1 antibody and normal mouse 131I-IgG, demonstrated that the localization of 131I-14AC1 antibody in glioma grafts in the result of specific antigen binding. The scintigrams using intact antibody without background subtraction provided adequate tumor visualization, but the activity in the blood was high even 96 h after injection. More rapid clearace of blood-pool radioactivity would possibly be achieved with F(ab')2 fragments. These in vivo glioma imaging studies, together with related in vitro binding tests, indicate the potential value of monoclonal antiglioma antibodies not only for clinical tumor radioimmunodetection, but also for the evaluation of immunotherapeutic approaches to the glioma disease of man.