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

Because of its high energy beta emissions and imageable gamma emissions, Re-188 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 Re-188 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 Re-188 with purification of immunoreactive Re-188-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 Re-188 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 Re-188 for immunoscintigraphy and immunotherapy of malignant diseases.