Comparative in vitro binding characteristics and biodistribution in tumor-bearing athymic mice of anti-ovarian carcinoma monoclonal antibodies.
The interactions of four monoclonal antibodies (OV-TL 3, OV-TL 16, OV-TL 30 and OC 125) with ovarian carcinoma cells (NIH: OVCAR-3) were compared in vitro as well as in a nude mouse model. The affinity constants of the antibodies ranged from 1.0 X 10(9) M-1 (OC 125) to 3 X 10(9) M-1 (OV-TL 30). The cell binding kinetics of the antibodies were studied in vitro: OV-TL 30 associated fastest (50% binding after 25 min), OV-TL 3 and OV-TL 16 associated more slowly (50% binding after 75 min), while the association of OC 125 was slowest (50% binding after 120 min). Dissociation rates of the antibodies also differed: OC 125 displayed the lowest dissociation rate (t1/2 = 360 min). The OV-TL antibodies showed a faster, biphasic dissociation characteristic. The biodistribution of the radioiodinated antibodies in NIH:OV-cAR-3 xenograft-bearing athymic mice, following intravenous injection, was compared. Highest tumor accumulation 48 h p.i. was found with OV-TL 3 (13.3 +/- 2.1% ID/g) and OV-TL 16 (11.0 +/- 2.0% ID/g), while the uptakes of OV-TL 30 and OC 125 were markedly lower (4.9 +/- 0.9% and 6.0 +/- 0.9% ID/g, respectively). The fact that in this experimental model the in vivo tumor accumulation of OV-TL 3 and OV-TL 16 was approximately twice as high as the tumor accumulation of OC 125 could not be fully ascribed to parameters of the antibodies determined in vitro (immunoreactive fraction, affinity constant, antigen density, association and dissociation rate). It is suggested that the antibodies OV-TL 3 and OV-TL 16 are suitable tools for clinical radioimmunodetection of ovarian carcinomas.
Boerman
O
O
Department of Cell Biology and Histology, University of Nijmegen, The Netherlands.
Massuger
L
L
Makkink
K
K
Thomas
C
C
Kenemans
P
P
Poels
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D002277:Carcinoma / Q000276:immunology*; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate