title: Technetium labeling of monoclonal antibodies with functionalized BATOs: 2. TcCl(DMG)3CPITC labeling of B72.3 and NP-4 whole antibodies and NP-4 F(ab')2.
abstract: BATO (boronic acid adduct of technetium dioximes) complexes, TcCl(dioxime)3BR, were prepared in which the boron substituent (R) was the protein-reactive 2-carboxy-4-phenyl isothiocyanate (CPITC). The 99Tc complexes, where the dioxime was either dimethylglyoxime (DMG) or cyclohexanedione dioxime (CDO), were prepared and characterized. The 99mTc complex TcCl(DMG)3CPITC was prepared from a freeze-dried kit and used to label B72.3 (anti-TAG.72) and NP-4 (anti-CEA) whole antibodies, and the NP-4 F(ab')2 fragment. SDS-PAGE electrophoresis indicated that the labeling reagent was strongly bound to antibody. The labeled antibodies displayed high binding to affinity columns and good tumor uptake in GW39 tumor-bearing mice.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903.
authors.forename: K E
authors.initials: KE
authors.lastname: Linder
authors.forename: M D
authors.initials: MD
authors.lastname: Wen
authors.forename: D P
authors.initials: DP
authors.lastname: Nowotnik
authors.forename: K
authors.initials: K
authors.lastname: Ramalingam
authors.forename: R M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: F
authors.initials: F
authors.lastname: Yost
authors.forename: R K
authors.initials: RK
authors.lastname: Narra
authors.forename: A D
authors.initials: AD
authors.lastname: Nunn
authors.forename: W C
authors.initials: WC
authors.lastname: Eckelman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology*; D001769:Blood; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006868:Hydrolysis; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D015609:Organotechnetium Compounds; D051381:Rats; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D015609:Organotechnetium Compounds; C047052:tumor-associated antigen 72; C074010:technetium Tc 99m tris(dimethylglyoxime)-3-carboxy-5-isothiocyanatophenylboronic acid