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  • Title: Biodistribution of anti-CEA F(ab')2 fragments conjugated with chelating polymers: influence of conjugate electron charge on tumor uptake and blood clearance.
    Author: Slinkin MA, Curtet C, Faivre-Chauvet A, Sai-Maurel C, Gestin JF, Torchilin VP, Chatal JF.
    Journal: Nucl Med Biol; 1993 May; 20(4):443-52. PubMed ID: 8504286.
    Abstract:
    F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb) were modified with three chain-terminal polylysine-based chelating polymers so as to carry different electron charges. Immunoreactive conjugates labeled with 111In up to a specific radioactivity of 120-140 microCi/micrograms were injected into nude mice bearing human colorectal carcinoma, and the biodistribution patterns were compared with each other and with that of an anti-CEA F(ab')2-DTPA control. Immunoconjugate modified with positively-charged polymer produced the highest tumor uptake [up to 20% injected dose per gram (ID/g)], with very significant non-specific radioactivity in normal organs (particularly kidneys). When modified with a polymer carrying only a slight negative charge, the immunoconjugate also produced fairly high tumor uptake (up to 18% ID/g), with much lower non-specific radioactivity in normal organs. Highly negatively-charged conjugate produced the lowest tumor uptake (up to 8% ID/g), whereas blood and whole-body clearances were the fastest but slower than those of conventionally labeled F(ab')2 mAb. The possible mechanisms for the effects described are discussed.
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