Intracellular processing of 99Tcm-antibody conjugates

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The catabolism of 99Tcm-antibody conjugates after internalization by B-cell lymphomas was investigated, using antibody LL1, an antibody to the MHC class II invariant chain which is internalized and catabolized very rapidly. Intact IgG antibodies were labelled with 99Tcm after mild reduction. The 99Tcm label was strongly retained within cells, similar to ‘residualizing’ labels such as 111In-diethylenetriamine pentaacetate (111In-DTPA), but different from a conventional iodine label. Unlike 111In-DTPA, 99Tcm was not retained in a low molecular weight form, but instead was found to be bound to a large number of different cellular proteins, and was retained in the cytoplasm rather than in lysosomes. Therefore, this form of 99Tcm represents a new paradigm of intracellular retention of a radiolabel.

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