Biodistribution of indium-111-labeled OC 125 monoclonal antibody after intraperitoneal injection in nude mice intraperitoneally grafted with ovarian carcinoma.
The purpose of this work was to study the biodistribution of 111In-labeled OC 125 monoclonal antibody (MAb) with known affinity for ovarian carcinomas in a nude mouse model grafted i.p. with a human ovarian cancer (NIH:OVCAR-3). Tumor uptake 24 h after i.p. injection was higher with intact 111In-labeled OC 125 MAb (28 +/- 7.44%ID/g) than with 111In-nonspecific immunoglobulin (6.86 +/- 1.35%ID/g). The kinetics of tumor uptake also differed, showing a plateau followed by a drop at Day 7 with 111In-OC 125 MAb and a decrease beginning at 24 h with 111In-nonspecific immunoglobulin. Tumor-to-normal tissue ratios ranged between 29.91 +/- 11.85 and 0.68 +/- 0.15 with 111In-OC 125 MAb and between 4.50 +/- 1.06 and 0.53 +/- 0.04 with 111In-nonspecific immunoglobulin according to the normal tissues and the time points considered. Tumor uptake 2 h after injection was the same for F(ab')2 fragments as for intact MAb, whereas maximum uptake at 24 h (18.76 +/- 4.62%ID/g) was lower and was followed by a decrease at Day 4. Tumor-to-normal tissue ratios were in the same range, except for the tumor to blood ratio which was higher and the tumor to kidney ratio which was lower at 24 and 96 h. Maximum tumor uptake was higher after i.p. (30.77 +/- 4.76%ID/g) than i.v. (14.59 +/- 2.70%ID/g) injection. Instead of attaining the plateau noted after i.p. injection, tumor uptake after i.v. injection remained low at 2 h (2.11 +/- 1.66%ID/g), reaching its peak only after 96 h. 131I-OC 125 injected i.p., which reached maximum tumor uptake at 2 h (13.53 +/- 4.25%ID/g), showed tumor-to-tissue ratios ranging between 15.98 +/- 2.63 and 0.96 +/- 0.86, i.e., not very different from those with 111In. After i.p. injection of a radiolabeled colloid solution, maximum tumor uptake was reached at 96 h (20.22 +/- 5.35%ID/g), but with very high nonspecific uptake in liver (31.06 +/- 6.22%ID/g) and spleen (55.23 +/- 14.11%ID/g). These results indicate high, selective tumor uptake of 111In-OC 125 after i.p. injection and demonstrate the feasibility of i.p. radioimmunotherapy of ovarian carcinomas.
Thédrez
P
P
Unité 211 INSERM, Faculté de Médecine, Nantes, France.
Saccavini
J C
JC
Nolibé
D
D
Simoen
J P
JP
Guerreau
D
D
Gestin
J F
JF
Kremer
M
M
Chatal
J F
JF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D007205:Indium Radioisotopes; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007205:Indium Radioisotopes