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  • Title: A comparison of 4 radionuclides conjugated to antibodies for single-cell kill.
    Author: Michel RB, Brechbiel MW, Mattes MJ.
    Journal: J Nucl Med; 2003 Apr; 44(4):632-40. PubMed ID: 12679410.
    Abstract:
    UNLABELLED: We previously found that (67)Ga was more potent and more specific in single-cell kill than other Auger electron emitters and beta-particle emitters, using an anti-CD74 antibody (Ab) (major histocompatibility complex [MHC] class II invariant chain). Because anti-CD74 Abs follow an unusual processing pathway, with rapid delivery in very large amounts to lysosomes, it was important to determine if similar results would be obtained with other, more typical Abs. METHODS: Target cells were Raji B-lymphoma cells, and the Abs tested were antimature MHC class II antigen (lacking the invariant chain) and anti-CD20, both of which react with high-density antigens. Labeling was with (125)I or (131)I, by conventional iodination; with (111)In using the chelator benzyl-diethylenetriaminepentaacetic acid; or with (67)Ga using the chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid. Abs were incubated with the cells for 2 d, uptake of radioactivity was assayed at various times, and toxicity was assayed primarily by a clonogenic assay. The fraction surviving was plotted versus cumulative disintegrations per cell to determine relative potency. RESULTS: The ranking of the radionuclides for potency was (131)I > (67)Ga > (125)I > (111)In. (67)Ga was approximately 2- to 3-fold more potent than (111)In. This was very similar to previous results with anti-CD74. Dosimetry calculations were generally consistent with the level of toxicity observed. In previous studies of nonspecific toxicity, the order of ranking was the same. CONCLUSION: The subcellular location of the bound Ab (whether on the cell surface or the cytoplasm) does not appear to be an important variable in the choice of radionuclide for single-cell kill. (67)Ga is a promising radionuclide for killing micrometastases, for high-density target antigens, but methods for achieving higher specific activity are required to fully exploit this approach. Each of the 4 radionuclides tested has certain advantages, and further studies are required to select the optimal radionuclide for a particular purpose.
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