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Title: Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination

Abstract

The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-(125I/131I)iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-(125I/131I)iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-(131I)iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with themore » Fab conjugate of 7b indicated that there was {approximately} a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate.« less

Authors:
;  [1]
  1. NeoRx Corporation, Seattle, WA (USA)
Publication Date:
OSTI Identifier:
5398697
Resource Type:
Journal Article
Journal Name:
Bioconjugate Chemistry; (United States)
Additional Journal Information:
Journal Volume: 1:2; Journal ID: ISSN 1043-1802
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; MONOCLONAL ANTIBODIES; TISSUE DISTRIBUTION; REAGENTS; CHEMICAL PREPARATION; COMPARATIVE EVALUATIONS; IODINATION; IODINE 131; LABELLING; MICE; NUCLEAR MAGNETIC RESONANCE; PRECURSOR; TRACER TECHNIQUES; ANIMALS; ANTIBODIES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CHEMICAL REACTIONS; DAYS LIVING RADIOISOTOPES; DISTRIBUTION; HALOGENATION; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; MAGNETIC RESONANCE; MAMMALS; NUCLEI; ODD-EVEN NUCLEI; RADIOISOTOPES; RESONANCE; RODENTS; SYNTHESIS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Hadley, S W, and Wilbur, D S. Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination. United States: N. p., 1990. Web. doi:10.1021/bc00002a011.
Hadley, S W, & Wilbur, D S. Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination. United States. https://doi.org/10.1021/bc00002a011
Hadley, S W, and Wilbur, D S. 1990. "Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination". United States. https://doi.org/10.1021/bc00002a011.
@article{osti_5398697,
title = {Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination},
author = {Hadley, S W and Wilbur, D S},
abstractNote = {The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-(125I/131I)iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-(125I/131I)iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-(131I)iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was {approximately} a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate.},
doi = {10.1021/bc00002a011},
url = {https://www.osti.gov/biblio/5398697}, journal = {Bioconjugate Chemistry; (United States)},
issn = {1043-1802},
number = ,
volume = 1:2,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 1990},
month = {Thu Mar 01 00:00:00 EST 1990}
}