Purification by affinity chromatography with anti-idiotypic monoclonal antibodies of immunoreactive monoclonal antibodies following labeling with 188Re.

Abstract

Because of its high energy beta emissions and imageable gamma emissions, 188Re represents an attractive isotope to radiolabel monoclonal antibodies (mAb) recognizing human tumor-associated antigens for radioimaging and radioimmunotherapy in patients with malignant diseases. The application of 188Re is, however, hindered by the denaturation of a sizable proportion of antibody molecules during the labeling process. To overcome this problem, we have combined radiolabeling of mAb with 188Re with purification of immunoreactive 188Re-labeled mAb by affinity chromatography over columns of anti-idiotypic (anti-id) mAb. Utilizing the anti-high-molecular-weight melanoma-associated antigen (HMW-MAA) mAb 763.74 as a model system, we found that the immunoreactivity of mAb 763.74 labeled with 188Re to a specific activity of 1 mCi/mg increased from about 50% to at least 80% following passage over columns of immobilized anti-id mAb. Moreover, between 90-100% of immunoreactive mAb contained in radiolabeled preparations could be recovered from anti-id mAb columns. These results indicate that the procedure we have described may facilitate the application of 188Re for immunoscintigraphy and immunotherapy of malignant diseases.