N-succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate: synthesis and potential utility for the radioiodination of monoclonal antibodies.
N-succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate (MATE) was synthesized in two steps from 4-methyl-3-iodobenzoic acid. Radioiododestannylation of MATE proceeded more slowly than N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE), but for reaction periods of 10 min or more, identical yields were obtained. Paired-label biodistribution studies were performed in mice with an intact monoclonal antibody and an F(ab')2 fragment labeled using MATE, ATE and Iodogen. Thyroid uptake with MATE was low, comparable to that seen with ATE, and considerably lower than that observed when the Iodogen method was used. With the F(ab')2 fragment, kidney uptake using MATE was 8-fold higher than that observed when either the ATE or Iodogen methods were used.
Department of Radiology, Duke University Medical Center, Durham, NC 27710.
P K
PK
Garg
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S
Garg
M R
MR
Zalutsky
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001565:Benzoates / Q000138:chemical synthesis*; D004355:Drug Stability; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism; D000922:Immunotoxins / Q000378:metabolism / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000627:therapeutic use; D007463:Iodobenzoates / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D013388:Succinimides / Q000737:chemistry; D014018:Tissue Distribution; D014220:Trialkyltin Compounds / Q000138:chemical synthesis*
D000911:Antibodies, Monoclonal; D001565:Benzoates; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D007463:Iodobenzoates; D013388:Succinimides; D014220:Trialkyltin Compounds; C081498:N-succinimidyl 4-methyl-3-iodobenzoate; C081497:N-succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate; C062337:N-succinimidyl 3-iodobenzoate