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.
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.
Linder
K E
KE
Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903.
Wen
M D
MD
Nowotnik
D P
DP
Ramalingam
K
K
Sharkey
R M
RM
Yost
F
F
Narra
R K
RK
Nunn
A D
AD
Eckelman
W C
WC
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
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