Technetium labeling of monoclonal antibodies with functionalized BATOs. 1. TcCl(DMG)3PITC.
BATO (boronic acid adduct of technetium dioximes) complexes, TcCl(dioxime)3BR, were prepared in which the boron substituent (R) was the protein-reactive m-phenyl isothiocyanate (PITC). The 99TcCl(dioxime)3PITC complexes [dioxime = dimethylglyoxime (DMG) or cyclohexanedione dioxime (CDO)] were prepared from 99Tc(dioxime)3(mu-OH)SnCl3 and characterized. The X-ray crystal structure of 99TcCl(DMG)3PITC was determined. The 99mTc complexes were prepared from 99mTcO4- in a process using a freeze-dried kit, either in a one-step procedure or via 99mTcCl(dioxime)3. Initial labeling studies with 99mTcCl(dioxime)3PITC were performed on glycine and polylysine and, subsequently, on mouse IgG and the B72.3 monoclonal antibody. Covalent attachment of 99mTcCl(DMG)3PITC to B72.3 was demonstrated by SDS-PAGE electrophoresis. B72.3 labeled with 99mTcCl(DMG)3PITC displayed high binding to a TAG 72 affinity column and had a distribution in normal mice similar to that reported for iodine-labeled B72.3.
Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903.
K E
KE
Linder
M D
MD
Wen
D P
DP
Nowotnik
M F
MF
Malley
J Z
JZ
Gougoutas
A D
AD
Nunn
W C
WC
Eckelman
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D001897:Boronic Acids; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000302:isolation & purification; D017879:Isothiocyanates; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013667:Technetium / Q000737:chemistry; D013861:Thiocyanates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014018:Tissue Distribution; D014961:X-Ray Diffraction
D000911:Antibodies, Monoclonal; D001897:Boronic Acids; D007074:Immunoglobulin G; D017879:Isothiocyanates; D015609:Organotechnetium Compounds; D013861:Thiocyanates; C071638:TcCl 99m (dioxime)(3) 3-phenylisothiocyanate; C071639:TcCl 99m (cyclohexanedione dioxime)(3) 3-phenylisothiocyanate; D013667:Technetium