Biodistribution of iodine-125 and indium-111 labeled OV-TL 3 intact antibodies and F(ab')2 fragments in tumor-bearing athymic mice.
The monoclonal antibody OV-TL 3, directed against an ovarian carcinoma-associated antigenic determinant, was tested as a vehicle for radioimmunolocalization of ovarian carcinomas in athymic mice bearing NIH:OVCAR-3 xenografts. The biodistribution of intact. OV-TL 3 was compared with the distribution of OC 125. Tumor uptake with OV-TL 3 was significantly higher than with OC 125, and almost 7 times higher than with a non-specific control antibody (OV-TL 19). Administration of a mixture of intact OV-TL 3 and OC 125 did not improve tumor uptake in comparison with OV-TL 3 alone. Subsequently, intact OV-TL 3 and its F(ab')2 fragments were labeled with either 111In or 125I. The highest tumor uptake was obtained with 111In-labeled intact OV-TL 3 (14.7% ID/g, 48 hr p.i.). For both antibody forms uptake of 111In in liver, spleen and kidneys was very high. Furthermore, 111In cleared more slowly from most tissues than 125I. As a result, tumor/tissue ratios with 111In-labeled OV-TL 3 were lower than with 125I-labeled OV-TL 3. The highest tumor/tissue ratios (6.9 to 53) were obtained with 125I-labeled OV-TL 3 F(ab')2 fragments, 48 hr post injection. 111In-labeled OV-TL 3 F(ab')2 has already been shown to be a clinically useful label for the detection of ovarian cancer. The results of our comparative animal study suggest that these clinical results may even be improved by using 123I-labeled OV-TL 3 F(ab')2.
Massuger
L F
LF
Department of Obstetrics and Gynecology, University Hospital Nijmegen, The Netherlands.
Boerman
O C
OC
Corstens
F H
FH
Verheijen
R H
RH
Claessens
R A
RA
Poels
L G
LG
van den Broek
W J
WJ
Kenemans
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes