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 ovarian carcinoma cells. Since ovarian cancer is mainly limited to the peritoneal 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)I, (125)I and (123)I (for imaging). Seven patients were operated 2 days, 7 patients 6 days and 1 patient 3 days post-injection. Radioactivity was determined in blood, ascites and biopsies of tumor and of several normal tissues. No adverse events occurred. No anti-MOv18 responses were observed. The area under the blood activity vs. time curve (AUC) was significantly lower after i.p. injection for 2 and 6 days post-injection (p = 0.01 and p = 0.02, respectively). 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 ovarian 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 advantageous with respect to bone marrow toxicity since the AUC was significantly lower for the i.p. route. However, within 2 days post-injection, the blood clearance followed the same pattern for both routes.
Department of Obstetrics and Gynecology, University Hospital, Vrije Universiteit, Amsterdam, The Netherlands.
I
I
van Zanten-Przybysz
C F
CF
Molthoff
J C
JC
Roos
R H
RH
Verheijen
A
A
van Hof
M R
MR
Buist
H M
HM
Prinssen
W
W
den Hollander
P
P
Kenemans
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001706:Biopsy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007553:Isotope Labeling; D007700:Kinetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000601:surgery; D010053:Ovary / Q000378:metabolism; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes