Radioiodination of antibodies via N-succinimidyl 2,4-dimethoxy-3-(trialkylstannyl)benzoates.
We have previously shown that use of N-succinimidyl 3-iodobenzoate (SIB) for radioiodination of monoclonal antibodies (MAbs) decreases the loss of radioiodine in vivo compared to MAbs labeled by using conventional methods. Herein, the synthesis of N-succinimidyl 2,4-dimethoxy-3-(trialkylstannyl)benzoates (alkyl = Me, Bu) are described as is their use as precursors for the radiosynthesis of N-succinimidyl 2,4-dimethoxy-3-iodobenzoate (SDMIB). A MAb F(ab')2 fragment labeled with SDMIB retained its ability to bind specifically to tumor homogenates. Paired-label tissue distribution studies indicate that the thyroid uptake (an indicator of deiodination) of hydrolyzed SDMIB was about 20 times that of hydrolyzed SIB. In contrast, thyroid uptake for SDMIB, when conjugated to a MAb, was only 1.4-2.8 times that for SIB and was considerably lower than levels reported in the literature for MAbs labeled by using direct, electrophilic iodination methods. Although MAbs labeled with SDMIB are significantly more inert to dehalogenation than those labeled by conventional methods, compared to the original SIB reagent, addition of two methoxy groups decreased retention of label in vivo.
Vaidyanathan
G
G
Duke University Medical Center, Department of Radiology, Durham, North Carolina 27710.
Zalutsky
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal; D001565:Benzoates / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D007463:Iodobenzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D013388:Succinimides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013961:Thyroid Gland / Q000378:metabolism; D014018:Tissue Distribution; D014220:Trialkyltin Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014298:Trimethyltin Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D001565:Benzoates; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D007463:Iodobenzoates; D013388:Succinimides; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C069574:N-succinimidyl-2,4-dimethoxy-3-(tributylstannyl)benzoate; C069573:N-succinimidyl-2,4-dimethoxy-3-(trimethylstannyl)benzoate; C069575:N-succinimidyl-2,4-dimethoxy-3-iodobenzoate; C038262:3-iodobenzoic acid; C062337:N-succinimidyl 3-iodobenzoate