| Abstract: |
We demonstrated previously that human B-cell lymphomas were effectively and specifically killed in vitro by an antibody to CD74 (LL1) linked to (111)ln or other Auger electron emitters. This study was intended to more accurately compare the potency and specificity of 3 Auger electron emitters, (111)ln, Ga-67, and I-125, and to evaluate beta -particle emitters, I-131 and Y-90. The unique property of LL1 is its high level of intracellular uptake. Methods: Raji B-lymphoma cells were incubated with serial dilutions of the radiolabeled Abs for 2 d and then monitored for cell growth by 2 assays: a cell counting assay and a clonogenic assay. The uptake of radioactivity per cell was monitored at various time points, and the radiation dose was calculated using published S values for radioactivity located in the cytoplasm. Both specific and nonspecific toxicity were evaluated. Results: The beta -particle emitters had considerably higher levels of nonspecific toxicity than the Auger electron emitters, but both I-131 and Y-90, and particularly I-131, still had high levels of specificity. Both of these results were consistent with dosimetry calculations. Relative to the delivered disintegrations per cell, I-131 and Ga-67 were the most potent of the radionuclides tested, with I-125 and In-111 being significantly weaker and Y-90 being intermediate. The high potency of Ga-67, together with its low nonspecific toxicity, caused this radionuclide to have the highest specificity index. Conclusion: When delivered by Ab LL1, both Auger electron and beta -particle emitters can produce specific and effective toxicity. The choice of the optimal radionuclide for therapy may depend on the ease and efficiency of labeling, the specific activity obtained, the nature of the tumor being targeted, and other factors, but the high specificity indices of the Auger electron emitters may be an advantage. |
