title: Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma.
abstract: In clinical studies we have evaluated a unique monoclonal antibody-based drug delivery system, a bifunctional antibody designed to deliver imaging or therapeutic agents, such as radioisotopes, drugs, or biologics, to tumor cells, while minimizing the dose to normal tissue. The bifunctional antibody, with one specificity to a tumor-associated antigen (carcinoembryonic antigen) and another specificity to a hapten, is injected and allowed to localize at a tumor site for 4 days. A hapten, tagged with a radioisotope, is subsequently injected for delivery to and capture by the prelocalized antibody at the tumor site. In studies reported here, the sulfhydryl groups of Fab' fragments of ZCE-025 and CHA-255 were linked with bis-maleimidomethyl ether to form an F(ab')2 bifunctional antibody coupled by a stable thioether linkage. EOTUBE, a hydroxyethylthiourido derivative of benzyl EDTA, was used as the hapten carrier of 111In. Fourteen patients 62-82 years old with recurrent or metastatic adenocarcinoma of the colon were studied. Twenty of 21 known lesions were imaged, and eight of nine new lesions were confirmed. With this fundamentally new approach to drug delivery, clearance from normal tissue is rapid, and high tumor:normal tissue ratios are expeditiously achieved.
authors.affiliation: Loma Linda University Medical Center, California 92354.
authors.forename: D R
authors.initials: DR
authors.lastname: Stickney
authors.forename: L D
authors.initials: LD
authors.lastname: Anderson
authors.forename: J B
authors.initials: JB
authors.lastname: Slater
authors.forename: C N
authors.initials: CN
authors.lastname: Ahlem
authors.forename: G A
authors.initials: GA
authors.lastname: Kirk
authors.forename: S A
authors.initials: SA
authors.lastname: Schweighardt
authors.forename: J M
authors.initials: JM
authors.lastname: Frincke
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002614:Chelating Agents / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D003432:Cross-Linking Reagents; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000276:immunology / Q000493:pharmacokinetics; D006241:Haptens; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D008875:Middle Aged; D011877:Radionuclide Imaging
chemical_list: D000906:Antibodies; D002272:Carcinoembryonic Antigen; D002614:Chelating Agents; D003432:Cross-Linking Reagents; D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; C071971:EOTUBE; D004492:Edetic Acid