Effect of acetylation on monoclonal antibody ZCE-025 Fab': distribution in normal and tumor-bearing mice.
Studies were performed to determine in vitro and in vivo effects of acetylation on Fab' fragments of ZCE-025, a monoclonal anti-CEA antibody. Isoelectric focusing revealed a drop in isoelectric point of 1.7 pI units following acetylation. Biodistribution studies of acetylated and nonacetylated [111In]Fab' were performed in normal BALB/c mice and in nude mice bearing the T-380 CEA-producing human colon tumor. The acetylated fragments remained in the vascular compartment longer and had significantly diminished renal uptake of 111In compared to controls. While acetylation itself effected a 50% drop in immunoreactivity, tumor uptake of the acetylated and nonacetylated 111In-labeled Fab' fragments was comparable, with the exception of one data point, through 72 h.
Tarburton
J P
JP
Department of Nuclear Medicine, Veterans Administration Medical Center, San Diego, CA 92161.
Halpern
S E
SE
Hagan
P L
PL
Sudora
E
E
Chen
A
A
Fridman
D M
DM
Pfaff
A E
AE
D000107:Acetylation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D007525:Isoelectric Focusing; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes