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Radiohalogenation of a monoclonal antibody using an N-succinimidyl 3-(tri-n-butylstannyl)benzoate intermediate.

Publication ,  Journal Article
Zalutsky, MR; Narula, AS
Published in: Cancer Res
March 15, 1988

N-Succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE) was elevated for its utility in the radiohalogenation of monoclonal antibodies. The F(ab')2 fragment of monoclonal antibody OC 125 was labeled with 125I using the ATE reagent and with 131I using a conventional electrophilic iodination method (Iodogen). N-Succinimidyl 3-[125I]iodobenzoate was synthesized from ATE in greater than 90% yield and purified using a disposable silica gel cartridge. About 60-65% of the radioiodinated product was coupled to the F(ab')2 fragment after a 30-min reaction. Two procedures were investigated, one involving exposure of antibody to 35 nmol of ATE and the other to 240 nmol of ATE. Using Scatchard analyses, affinity constants for binding to CA 125 antigen for OC 125 F(ab')2 labeled using the low ATE, Iodogen, and high ATE procedures were determined to be (5.2 +/- 1.0) x 10(10), (2.5 +/- 0.9) x 10(10), and (4.2 +/- 2.4) x 10(9) M-1, respectively. Paired-label studies in athymic mice bearing OVCAR-3 tumors treated with injections of antibody labeled via both ATE and Iodogen demonstrated that use of the ATE method (a) reduced thyroid uptake to less than 0.1% of the injected dose, more than 100 times less than that observed with Iodogen; (b) resulted in more rapid clearance of activity from normal tissues; and (c) with the low ATE preparations, increased the uptake of radioactivity in tumor from 27 to 49%. At 96 h, tumor:tissue ratios were generally at least 4-fold higher when antibody was labeled via ATE. These results suggest that the ATE method may be a valuable approach for the radiohalogenation of antibodies.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 15, 1988

Volume

48

Issue

6

Start / End Page

1446 / 1450

Location

United States

Related Subject Headings

  • Trialkyltin Compounds
  • Tissue Distribution
  • Oncology & Carcinogenesis
  • Mice, Inbred BALB C
  • Mice
  • Isotope Labeling
  • Iodobenzoates
  • Iodine Radioisotopes
  • Immunoglobulin Fab Fragments
  • Benzoates
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zalutsky, M. R., and A. S. Narula. “Radiohalogenation of a monoclonal antibody using an N-succinimidyl 3-(tri-n-butylstannyl)benzoate intermediate.Cancer Res 48, no. 6 (March 15, 1988): 1446–50.
Zalutsky, M. R., and A. S. Narula. “Radiohalogenation of a monoclonal antibody using an N-succinimidyl 3-(tri-n-butylstannyl)benzoate intermediate.Cancer Res, vol. 48, no. 6, Mar. 1988, pp. 1446–50.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 15, 1988

Volume

48

Issue

6

Start / End Page

1446 / 1450

Location

United States

Related Subject Headings

  • Trialkyltin Compounds
  • Tissue Distribution
  • Oncology & Carcinogenesis
  • Mice, Inbred BALB C
  • Mice
  • Isotope Labeling
  • Iodobenzoates
  • Iodine Radioisotopes
  • Immunoglobulin Fab Fragments
  • Benzoates