Devys A, Thedrez P, Gautherot E, Faivre-Chauvet A, Saï-Maurel C, Rouvier E, Auget J L, Barbet J, Chatal J F
Unité 211 INSERM, Institut de Biologie, Nantes, France.
Int J Cancer. 1996 Sep 17;67(6):883-91. doi: 10.1002/(SICI)1097-0215(19960917)67:6<883::AID-IJC20>3.0.CO;2-1.
In the perspective of radioimmunotherapy (RIT) of micrometastases, we compared, in multicell spheroids (MS), the uptake and retention kinetics of 125I-F(ab)'2 F6 anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), and the affinity enhancement system (AES) using an anti-CEA/anti-DTPA-indium bispecific antibody (BsMAb) and a 125I-labeled di-DTPA-In-tyrosine-lysine bivalent hapten. We used MS of colorectal tumor cell lines expressing CEA strongly (LS 174T), weakly (HT-29) or not at all (HRT-18). Uptake and retention kinetics of 125I-F(ab)'2 F6 and 125I-BsMAb used alone gave similar results. The highest uptake values, obtained with LS 174T MS, were slightly lower with AES than with 125I-F(ab)'2 F6. However, effective retention half-lives were longer for AES than for 125I-F(ab)'2 F6 or for 111In-labeled monovalent hapten after pre-incubation of spheroids with BsMAb. Autoradiography showed the same slow and heterogeneous distribution of 125I-F(ab)'2 F6 and 125I-BsMAb. These results indicate that the 2-step technique is more favorable for RIT: uptake values were approximately the same but uptake kinetics were more rapid, and retention half-life was longer than with the one-step technique.
从微转移灶的放射免疫治疗（RIT）角度出发，我们在多细胞球体（MS）中比较了125I-F(ab)'2 F6抗癌胚抗原（CEA）单克隆抗体（MAb）以及使用抗CEA/抗二乙三胺五乙酸铟双特异性抗体（BsMAb）和125I标记的二-DTPA-In-酪氨酸-赖氨酸二价半抗原的亲和增强系统（AES）的摄取和保留动力学。我们使用了高表达CEA（LS 174T）、低表达CEA（HT-29）或不表达CEA（HRT-18）的结肠肿瘤细胞系的MS。单独使用125I-F(ab)'2 F6和125I-BsMAb的摄取和保留动力学得到了相似的结果。LS 174T MS获得的最高摄取值，使用AES时略低于使用125I-F(ab)'2 F6时。然而，在球体与BsMAb预孵育后，AES的有效保留半衰期比125I-F(ab)'2 F6或111In标记的单价半抗原更长。放射自显影显示125I-F(ab)'2 F6和125I-BsMAb具有相同的缓慢且不均匀的分布。这些结果表明，两步技术对RIT更有利：摄取值大致相同，但摄取动力学更快，并且保留半衰期比一步技术更长。
