Effect of mass of 111In-benzyl-EDTA monoclonal antibody on hepatic uptake and processing in mice.
In patients, the pharmacokinetic behavior of murine monoclonal antibodies has been observed to vary with the amount of antibody administered. It has been suggested that this reflects human recognition of the foreign mouse protein. We have found that the amount of antibody administered also influenced pharmacokinetic behavior when murine monoclonal antibody was administered to mice. p-Isothiocyanatobenzyl-EDTA, a new chelator which forms complexes with 111In that are stable in vivo, was conjugated to Lym-1, a murine anti-Burkitt's lymphoma monoclonal antibody. The pharmacokinetics of two doses (20 and 0.2 micrograms) of the 111In labeled radiopharmaceutical were studied in non-tumor bearing BALB/c mice. About 20% (0.04 microgram) of the 0.2-microgram dose, compared with 8% (1.6 micrograms) of the 20-micrograms dose, was found in the liver at 48 h after injection. Both doses demonstrated a biological half-life of approximately 120 h. At least 75% of the 111In was excreted by the kidneys, and essentially all 111In in the urine remained chelated by the EDTA portion of p-isothiocyanatobenzyl-EDTA. From these observations of a dose dependent uptake of this radiopharmaceutical by the liver we conclude that there is a recognition phenomenon in mice for this murine monoclonal antibody.
Adams
G P
GP
Department of Internal Medicine, University of California Davis Medical Center, Sacramento 95817.
DeNardo
S J
SJ
Deshpande
S V
SV
DeNardo
G L
GL
Meares
C F
CF
McCall
M J
MJ
Epstein
A L
AL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D004306:Dose-Response Relationship, Immunologic; D004492:Edetic Acid / Q000008:administration & dosage*; D005260:Female; D007205:Indium Radioisotopes; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D004492:Edetic Acid