CATABOLISM OF RADIOIODINATED MURINE MONOCLONAL-ANTIBODY F(AB')(2) FRAGMENT LABELED USING N-SUCCINIMIDYL 3-IODOBENZOATE AND IODOGEN METHODS

被引:31
作者
GARG, PK [1 ]
ALSTON, KL [1 ]
ZALUTSKY, MR [1 ]
机构
[1] DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710
关键词
D O I
10.1021/bc00034a020
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The F(ab')(2) fragment of monoclonal antibody (MAb) Me1-14 was labeled with I-125 using the Iodogen method and by reaction with N-succinimidyl 3-[I-125]iodobenzoate (SIE). The labeled catabolites generated after exposure to tissue homogenates in vitro and following administration of labeled F(ab')(2) into normal mice were investigated by size-exclusion HPLC, gel electrophoresis, and reverse-phase HPLC. Rapid conversion of F(ab')(2) to Fab was observed with both labeling methods. With F(ab')(2) labeled using the Iodogen method, the primary low molecular weight catabolites appeared to be [I-125]iodide and, to a lesser extent, mono[I-125]iodotyrosine. With SIB, [I-125]iodide and [I-125]iodobenzoic acid (IBA) as well as the glycine and lysine conjugates of IBA were all observed. Differences in low molecular weight catabolic products could explain the more rapid normal tissue clearance with MAbs and MAb fragments labeled with SIE compared with those labeled using iodogen.
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页码:493 / 501
页数:9
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