Enhanced kidney clearance with an ester-linked 99mTc-radiolabeled antibody Fab'-chelator conjugate.
Bifunctional chelators for labeling antibodies with 99mTc based on the N3S core of (mercaptoacetyl)-triglycine having ester or amide linking moieties were synthesized and site-specifically attached to the sulfhydryl groups of the Fab' fragment of antimyosin. Protein labeling was quantitative after 15 min; postlabeling purification was not necessary. The radiolabeled conjugates exhibited no loss of immunoreactivity. Under basic conditions, the ester-linked conjugate lost 95% of the radiolabel in the form of the 99mTc complex of (mercaptoacetyl)triglycine as determined by RP-HPLC, while the radioactivity in the amide-linked conjugate remained completely bound to the protein. In a mouse biodistribution study, the ester-linked conjugate showed a 2-fold enhancement in clearance from the kidney when compared to the amide-linked product.
Weber
R W
RW
Chemistry Research, Centocor, Incorporated, Malvern, Pennsylvania 19355.
Boutin
R H
RH
Nedelman
M A
MA
Lister-James
J
J
Dean
R T
RT
D000577:Amides; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000138:chemical synthesis*; D004952:Esters; D005260:Female; D007140:Immunoglobulin Fab Fragments; D007553:Isotope Labeling; D007668:Kidney / Q000378:metabolism*; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D015394:Molecular Structure; D009218:Myosins / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013667:Technetium; D014018:Tissue Distribution
D000577:Amides; D003432:Cross-Linking Reagents; D004952:Esters; D007140:Immunoglobulin Fab Fragments; D008301:Maleimides; D009842:Oligopeptides; C069583:5-(N-maleimido)-3-oxapentyl-(2-((3-carboxybenzoyl)thio)acetyl)glycyl-glycyl-glycinate; C069582:N-(5-maleimido-3-oxapentyl)(2-(3-carboxybenzoyl)thio)acetylglycyl-glycyl-glycinamide; D013667:Technetium; D009218:Myosins