Improved tumor targeting of rhenium-186-labeled anti-human high-MW melanoma-associated antigen monoclonal antibody 763.74 following purification with anti-idiotypic monoclonal antibody MK2-23

Because of its high-energy beta emissions and imageable gamma emissions, Re-186 represents an attractive isotope to radiolabel monoclonal antibodies (MAbs) recognizing human tumor-associated antigens (TAAs) for radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) of patients with malignant diseases, Application of Re-186, however, is hindered by the frequent denaturation of MAbs following exposure to the strong reducing conditions employed in the labeling procedures. To overcome this problem, we have utilized a direct labeling procedure and combined it with affinity chromatography over columns of immobilized anti-idiotypic (anti-id) MAbs which recognize idiotopes in the antigen-combining site of the radiolabeled MAb, The validity of the procedure was demonstrated with the anti-high-m.w. melanomaassociated antigen (HMW-MAA) MAb 763.74 and its corresponding anti-id MAb MK2-23. Utilizing this approach, MAb 763.74 was labeled to specific activities of 2.8 +/- 0.6 mCi/mg with Re-186. Furthermore, its immunoreactivity, which was reduced to about 30% following labeling with Re-186, was improved to about 50% by affinity chromatography over columns of anti-id MAb MK2-23, The improvement in immunoreactivity of Re-186 MAb 763.74 resulted in a significant(p < 0.05) increase in targeting to human melanoma tumors grown in nude mice and an increase in sensitivity of RIS. Our results suggest that direct labeling of anti-TAA MAb with Re-186 coupled with purification over affinity columns of anti-id MAb may facilitate the application of Re-186 to RIS and RIT. (C) 1998 Wiley-Liss, Inc.