Improved tumor targeting of rhenium-186-labeled anti-human high-m.w. 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, 186Re 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 186Re, 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. melanoma-associated 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 186Re. Furthermore, its immunoreactivity, which was reduced to about 30% following labeling with 186Re, was improved to about 50% by affinity chromatography over columns of anti-id MAb MK2-23. The improvement in immunoreactivity of 186Re 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 186Re coupled with purification over affinity columns of anti-id MAb may facilitate the application of 186Re to RIS and RIT.
Hamby
C V
CV
Department of Microbiology and Immunology, New York Medical College, Valhalla, 10595, USA. carl_hamby@nymc.edu
Chinol
M
M
Palestro
C J
CJ
Manzo
C
C
Ferrone
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000915:Antibody Affinity; D000951:Antigens, Neoplasm; D002846:Chromatography, Affinity; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008545:Melanoma / Q000000981:diagnostic imaging / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000276:immunology*; D009368:Neoplasm Transplantation; D011868:Radioisotopes; D011877:Radionuclide Imaging; D012211:Rhenium; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011868:Radioisotopes; D012211:Rhenium