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

Journal Article · Thu Mar 01 04:00:00 EST 1990 · Bioconjugate Chemistry; (United States)

DOI:https://doi.org/10.1021/bc00002a011· OSTI ID:5398697

Hadley, S W; Wilbur, D S ^[1]

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1. NeoRx Corporation, Seattle, WA (USA)

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.

• OSTI ID: 5398697
• Journal Information: Bioconjugate Chemistry; (United States), Journal Name: Bioconjugate Chemistry; (United States) Vol. 1:2; ISSN 1043-1802; ISSN BCCHE
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHEMICAL PREPARATION
CHEMICAL REACTIONS
COMPARATIVE EVALUATIONS
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
HALOGENATION
INTERMEDIATE MASS NUCLEI
IODINATION
IODINE 131
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLING
MAGNETIC RESONANCE
MAMMALS
MICE
MONOCLONAL ANTIBODIES
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
PRECURSOR
RADIOISOTOPES
REAGENTS
RESONANCE
RODENTS
SYNTHESIS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES