Non-covalent antibody-mediated drug delivery.
High background activity produces imaging problems when scanning with antibodies. The following work is directed towards reducing this background. The murine monoclonal antibody (MAb) CHA-255 selectively binds 111In-nitrobenzyl EDTA, a molecule referred to as a 'hapten'. Balb/c mice studies indicate that if the antibody is administered prior to the hapten, it predictably modifies the biodistribution and pharmacokinetics of the hapten. The pharmacokinetics for the hapten were proportional to antibody dose and inversely proportional to the time interval between injection of the antibody and the hapten. A hybrid MAb was produced by the enzymatic digestion of CHA-255 and ZCE-025, an anticarcinoembryonic antigen (CEA) MAb, followed by joining of the two via a thioether linkage. The result was a F(ab')2 with affinity for both CEA and the hapten. The pharmacokinetics of the hapten were again dependent upon the kinetics and distribution of the hybrid antibody. Data in tumour models are also presented for 111In-nitrobenzyl EDTA and 111In-thioureabenzyl EDTA (TUBE), a newer hapten. The data indicate that the antibody-hapten system is capable of targeting tumour quickly while normal tissue rapidly becomes depleted of radioactivity. We conclude that the hapten-antibody technique shows some advantages over directly labelled MAb as a targeting system.
Lollo
C
C
Department of Veterans Affairs Medical Center, San Diego, California 921161.
Halpern
S
S
Bartholomew
R
R
David
G
G
Hagan
P
P
D000818:Animals; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging*; D004492:Edetic Acid / Q000031:analogs & derivatives; D006241:Haptens; D006801:Humans; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D014018:Tissue Distribution
C078240:4-nitrobenzyl-EDTA; D006241:Haptens; D007205:Indium Radioisotopes; C089173:thioureabenzyl-EDTA; D004492:Edetic Acid