Radioimaging of experimental glioma grafts using F (ab')2-fragments of monoclonal antibodies.

Iodinated F (ab')2-fragments of monoclonal IgG2a-antibodies (McAbs) 14 AC1 raised against membrane components of an experimental rat glioma (79FR-G-41) were used for the radioimmunodetection of glioma xenografts in athymic mice. For gamma imaging, nude mice with intramuscular glioma grafts received 10-20 micrograms of 131I-labelled whole immunoglobulins and F (ab')2-fragments of the 14AC1 McAb, respectively, with an activity of 50-150 mu Ci (1.85-5.55 MBq). Scans obtained at 24, 48, 72 and 96 hours after injection demonstrated tumor accumulation of F (ab')2-fragments at 24 hours, and adequate tumor visualization without background subtraction at 48 hours. The rapid blood clearance of F (ab')2-fragments resulted in a whole body half life of 6 hours. Scintigrams using intact antibody provided comparable tumor localization at 96 hours, but also high bloodpool radioactivity and a half life period of more than 4 days. 131I-labelled normal mouse-IgG as control for non-specific uptake of immunoglobulins in the tumor revealed no tumor visualization at any time. Rapid tumor permeation, short blood clearance and a markedly reduced background radioactivity let F (ab')2-fragments appear superior to whole immunoglobulins in immunoscintigraphy, thus indicating their potential value for the improvement of radioimmunodiagnosis of glioma disease.