Labeling proteins using aryl iodide acylation agents: influence of meta vs para substitution on in vivo stability.
The effect of para vs meta substitution on the biological behavior of an intact antibody and an F(ab')2 fragment was investigated. Paired-label studies were performed using 81C6 IgG and OC 125 F(ab')2 labeled using the N-succinimidyl esters of both p-[125I]- and m-[131I]iodobenzoate as well as with the potential catabolites, p-[125I]- and m-[131I]iodobenzoic acid. In all 3 studies, up to 55% lower uptake of 131I in thyroid and stomach was observed, suggesting that the m-substituted species were more inert to dehalogenation in vivo.
Garg
P K
PK
Department of Radiology, Duke University Medical Center, Durham, NC 27710.
Slade
S K
SK
Harrison
C L
CL
Zalutsky
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D004355:Drug Stability; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D007463:Iodobenzoates / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000276:immunology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D007463:Iodobenzoates; D009363:Neoplasm Proteins; C062338:N-succinimidyl 4-iodobenzoate; C062337:N-succinimidyl 3-iodobenzoate