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Radiohalogenation of a Monoclonal Antibody Using an N-Succinimidyl 3-(Tri-n-butylstannyl)benzoate Intermediate¹

Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710

N-Succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE) was evaluated 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 >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 10¹⁰, (2.5 ± 0.9) x 10¹⁰, and (4.2 ± 2.4) x 10⁹ 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 <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.

¹ This work was supported in part by Grant CA 42324 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Duke University Medical Center, Box 3808, Durham, NC 27710.

Received 9/14/87. Revised 12/10/87. Accepted 12/16/87.

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