Intraperitoneal (IP) delivery of radiolabeled monoclonal antibody to IP-induced xenografts of human ovarian cancers

Ovarian cancers frequently metastasize intraperitoneally. This study was designed to evaluate the delivery of an anti-ovarian carcinoma monoclonal antibody (UMNMWR-2) after ip injection into mice with intraperitoneal innoculums of ovarian cancer (HTB-77). UMNMWR-2 is an IgG2a monoclonal produced by immunizing the foot pads of Balb/C mice with HTB-77 cells and fusing popliteal lymphocytes with the P3X63Ag 8.653 non-secreting myeloma. This antibody binds strongly to 3/3 ovarian carcinoma cell lines tested and only weakly to a panel of normal mononuclear cells. A control monoclonal IgG2a (225.28S) directed against melanoma and unreactive with the HTB-77 target cells was also used (a gift of Dr. B. Wilson). Athymic nude mice were innoculated with 10 million HTB77 cells. About 6 weeks later tumors were apparent at the injection site and in the parietal paritoneum-no small peritoneal studding was seen, the tumors being quite discrete. Four mice, so innoculated, were when their external tumors were visible, were given 15uCi of 131 I UM NMWR-2 antibody and 15uCi of 225.28S antibody ip. Animals were sacrificed with tissues and organs weighed and counted. Imaging was attempted using a gamma camera. Images were not satisfactory due to rapid deiodination of the I131 antibody. Despite this problem, there was a much higher tumor/blood ratio in the extraperitoneal tumor and intraperitoneal tumors for the UMNMWR-2 than the 225.28S (EP t/b=4.8 vs .3, and ip t/b=2.6 vs 64). No definite advantage was seen for the ip delivery route to the ip tumors vs the ep tumors at 4d. using this dosage scheme and the relatively focal ip tumors. Specific antibody accretion was demonstrated by both ip and ep tumors using the intraperitoneal approach to delivery, however.