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  • 1
    ISSN: 1619-7089
    Keywords: Indium-111 ; monoclonal Fab′ ; In vivo stability human ; 111-In Fab′ excretion pattern ; Electrophoresis ; Animal distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was conducted to investigate alterations that occur in an indium/111 Fab′ of a monoclonal antibody following its in vivo administration. Patients were infused with 111 In-Fab′ of the monoclonal antibody ZCE-025. Serum and urine specimens were collected from these patients. Starting materials, serum, urine and controls samples were studied by electrophoresis. Animal distribution studies were performed in normal Balb/c mice and, in some cases, nude mice bearing a carcinoembryonic antigen (CEA)/producing human colon tumour since the antibody targets CEA. The studies indicated that the molecule circulated almost totally intact for at least 4 h and to a considerable extent for 24 h, with some evidence for in vivo fragmentation by 24 h. Evidence was also obtained suggesting the formation of a high molecular weight species in some patients. Shortly after infusion, some of the 111In in the urine appeared as the intact Fab′, but within hours the majority migrated electro-phoretically as low molecular weight species. We conclude that while the majority of the 111In-Fab′ of this particular antibody remains intact and immunoreactive following its administration, the molecule is structurally changed to some degree shortly after its infusion into humans. Since each monoclonal antibody is unique, the degree and rapidity of degradation of its Fab′ in vivo could vary markedly from the above and possibly adversely effect its utility as a radiopharmaceutical.
    Type of Medium: Electronic Resource
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