Influence of the route of administration on targeting of ovarian cancer with the chimeric monoclonal antibody MOv18: I.v. vs. i.p.

MOv18 antibody binds the membrane folate receptor highly expressed on ovari an carcinoma cells. Since ovarian cancer is mainly limited to the peritonea l cavity, locoregional delivery of therapeutics can be an option. The same patient was injected i.v. and i.p. with c-MOv18 IgG labeled with different radionuclides. To study the kinetics of c-MOv18, patients were divided into 2 groups. Fifteen patients received c-MOv18 labeled with (131)1, (125)1 an d (123)1 (for imaging). Seven patients were operated 2 days, 7 patients 6 d ays and I patient 3 days post-injection. Radioactivity was determined in bl ood, ascites and biopsies of tumor and of several normal tissues. No advers e events occurred. No anti-MOv18 responses were observed. The area under th e blood activity vs. time curve (AUC) was significantly lower after i.p. in jection for 2 and 6 days post-injection (p = 0.01 and p = 0.02, respectivel y). At 2 days post-injection, a significant difference in tumor uptake was found in favor of the i.v. route of administration (4.9% and 2.4%ID/kg for i.v, and i.p., respectively; p < 0.0001), Uptake in solid tumor tissue in o varian cancer patients operated 6 days post-injection was not significantly different (p = 0.79) for both routes (3.8% and 3.9%ID/kg for i.v. and i.p. , respectively). In conclusion, no advantage could be demonstrated for the i.p. route with respect to tumor uptake. The i.p. route could be advantageo us with respect to bone marrow toxicity since the AUC was significantly low er for the i.p. route. However, within 2 days post-injection, the blood cle arance followed the same pattern for both routes. (C) 2001 Wiley-Liss, Inc.