Camera L, Kinuya S, Garmestani K, Pai L H, Brechbiel M W, Gansow O A, Paik C H, Pastan I, Carrasquillo J A
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
Nucl Med Biol. 1993 Nov;20(8):955-62. doi: 10.1016/0969-8051(93)90096-d.
Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with 111In, were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to-liver ratios increased from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for 111In-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for 111In-(1B4M)-B3. This was mainly the result of low liver accumulation of both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3, with only 2.48 +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for 111In-labeling of MAbs and that 111In-B3 may represent a promising radioimmunoimaging agent.
对与2-(对异硫氰酸苄基)-环己基-DTPA(CHX-B)或2-(对异硫氰酸苄基)-6-甲基-DTPA(1B4M)偶联并经¹¹¹In标记的单克隆抗体(MAb)B3在荷A431人表皮样癌异种移植瘤的裸鼠体内的生物分布及显像特性进行了评估。MAb B3是一种鼠IgG1κ，可与大多数癌大量表达的一种碳水化合物抗原发生反应。¹¹¹In-(CHX-B)-B3和¹¹¹In-(1B4M)-B3均显示出良好的肿瘤靶向性，在72小时观察到峰值，分别为27.6±7.6和25.4±1.7% ID/g(P>0.05)。还观察到高肿瘤与器官比值，且成像结果证实了这一点。特别是，¹¹¹In-(CHX-B)-B3的肿瘤与肝脏比值从24小时时的5.0±0.9增加到168小时时的9.2±2.0，¹¹¹In-(1B4M)-B3的该比值从4.5±0.6增加到8.9±3.5。这主要是由于¹¹¹In-(CHX-B)-B3和¹¹¹In-(1B4M)-B3在肝脏中的蓄积较低，在168小时时分别仅为2.48±0.46和2.5±0.9% ID/g(P>0.05)。我们的研究结果表明，CHX-B或1B4M均可成功用于MAb的¹¹¹In标记，且¹¹¹In-B3可能是一种有前景的放射免疫显像剂。
