Radiosensitizer conjugation to the carcinoma 19-9 monoclonal antibody
Borlinghaus, K.P.; Fitzpatrick, D.A.; Heindel, N.D.; Mattis, J.A.; Mease, B.A.; Schray, K.J.; Shealy, D.J.; Walton, H.L.; Woo, D.V.
Cancer Research 47(15): 4071-4075
1987
ISSN/ISBN: 0008-5472 PMID: 3496956 Document Number: 302437
Misonidazole was covalently conjugated (3-68 mol drug/mol antibody) to 19-9 monoclonal antibody directed against a colorectal carcinoma tumor-associated antigen as a method for targeting radiosensitizing agents. This attachment was accomplished by the mixed anhydride method using the hemisuccinate derivative of misonidazole. Evaluation of conjugates in vitro shows a loss of antibody binding activity with increasing loading levels; however, significant binding activity is retained even at relatively high sensitizer/antibody ratios. This observation was consistent in three binding assays: a competitive radioimmunoassay; an enzyme immunoassay; and an affinity column assay. From these studies, it was concluded that the optimal loading factor for misonidazole-antibody conjugates, when it is used for immunochemotherapy lies between 8 and 15. In vitro release studies indicated that conjugates are hydrolytically stable (t1/2 = 4 days) under physiological conditions.