Govindan S V, Goldenberg D M, Elsamra S E, Griffiths G L, Ong G L, Brechbiel M W, Burton J, Sgouros G, Mattes M J
Immunomedics, Inc., Morris Plains, New Jersey, USA.
J Nucl Med. 2000 Dec;41(12):2089-97.
We demonstrated previously that human B-cell lymphomas were effectively and specifically killed in vitro by an antibody to CD74 (LL1) linked to (111)In or other Auger electron emitters. This study was intended to more accurately compare the potency and specificity of 3Auger electron emitters, (111)In, 67Ga, and 125I, and to evaluate beta-particle emitters, 131I and 90Y. The unique property of LL1 is its high level of intracellular uptake.
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.
The beta-particle emitters had considerably higher levels of nonspecific toxicity than the Auger electron emitters, but both 131I and 90Y, and particularly 131I, still had high levels of specificity. Both of these results were consistent with dosimetry calculations. Relative to the delivered disintegrations per cell, 131I and 67Ga were the most potent of the radionuclides tested, with 125I and (111)In being significantly weaker and 90Y being intermediate. The high potency of 67Ga, together with its low nonspecific toxicity, caused this radionuclide to have the highest specificity index.
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.
我们之前证明，与铟-111（¹¹¹In）或其他俄歇电子发射体相连的抗CD74抗体（LL1）能在体外有效且特异性地杀伤人类B细胞淋巴瘤。本研究旨在更准确地比较三种俄歇电子发射体¹¹¹In、镓-67（⁶⁷Ga）和碘-125（¹²⁵I）的效力和特异性，并评估β粒子发射体碘-131（¹³¹I）和钇-90（⁹⁰Y）。LL1的独特性质是其在细胞内的高摄取水平。
用放射性标记抗体的系列稀释液孵育拉吉（Raji）B淋巴瘤细胞2天，然后通过两种检测方法监测细胞生长：细胞计数检测和克隆形成检测。在不同时间点监测每个细胞的放射性摄取，并使用已发表的细胞质中放射性的S值计算辐射剂量。评估特异性和非特异性毒性。
β粒子发射体的非特异性毒性水平比俄歇电子发射体高得多，但¹³¹I和⁹⁰Y，尤其是¹³¹I，仍具有高特异性水平。这两个结果均与剂量学计算一致。相对于每个细胞传递的衰变次数，¹³¹I和⁶⁷Ga是所测试的放射性核素中效力最强的，¹²⁵I和¹¹¹In明显较弱，⁹⁰Y居中。⁶⁷Ga的高效力及其低非特异性毒性导致该放射性核素具有最高的特异性指数。
当通过抗体LL1传递时，俄歇电子发射体和β粒子发射体均可产生特异性和有效的毒性。治疗中最佳放射性核素的选择可能取决于标记的难易程度和效率、获得的比活度、靶向肿瘤的性质及其他因素，但俄歇电子发射体的高特异性指数可能是一个优势。
