Kraeber-Bodéré F, Mishra A, Thédrez P, Faivre-Chauvet A, Bardiès M, Imai S, Le Boterff J, Chatal J F
INSERM Research Unit 211, 9 quai Moncousu, Nantes, France.
Eur J Nucl Med. 1996 May;23(5):560-7. doi: 10.1007/BF00833392.
The use of samarium-153 in the context of radioimmunotherapy of cancers has been limited by the instability of antibody labelling, which produces high uptake concentrations in liver and bone. This study compares the pharmacokinetics and biodistribution of 153Sm-labelled OC125 monoclonal antibody, in whole or F(ab')2 fragment form and with diethylene triamine penta-acetic acid (DTPA) or 6-p-isothiocyanatobenzyl diethylene triamine penta-acetic acid (CITCDTPA) coupling, in nude mice grafted subcutaneously with an ovarian adenocarcinoma line (SHIN-3) expressing CA125 antigen. The specific activity of the immunoconjugates was 18.5-55.5 MBq/mg, and their immunoreactivity exceeded 65%. With 153Sm-DTPA-OC125F(ab')2, the stability study in serum indicated that 50% of the metal remained bound to the antibody. The pharmacokinetic study showed a retention half-life of 25.1 h and blood clearance of 0.72 ml/h. The biodistribution study indicated tumour uptake of 4.53%+/-0.49% of injected activity per gram (%ID/g) at 24 h and tumour-to-liver and tumour-to-bone ratios of 0.23+/-0.02 and 1.54+/-0.49 respectively at 24 h. With 153Sm-CITCDTPA-OC125F(ab')2, serum stability was greater (87% of the metal remaining bound to the antibody), retention half-life was 22.25 h and blood clearance was 2.23 ml/h. Tumour was better targeted (8.30%+/-3.56%ID/g at 24 h), and tumour-to-liver and tumour-to-bone ratios were 1.17+/-0.36 and 7.08+/-3.09 respectively at 24 h. However, renal retention remained elevated (29.76%+/-9. 41%ID/g at 24 h). With intact IgG, renal uptake decreased (1.41%+/-0. 49%ID/g at 24 h), but tumour uptake was lower than with fragments (1. 46%+/-0.58%ID/g at 24 h). Liver uptake was higher (tumour-to-liver ratio 0.10+/-0.05), and blood clearance was slower. The stability and distribution of 153Sm-CITCDTPA were more favourable than those of 153Sm-DTPA for application in radioimmunotherapy. Quantitative analysis performed using digitized images obtained by conventional autoradiography and the imaging plate system indicated that the latter system is suitable for biodistribution studies of immunoconjugates.
钐 - 153在癌症放射免疫治疗中的应用受到抗体标记不稳定的限制，这种不稳定性会导致肝脏和骨骼中出现高摄取浓度。本研究比较了以完整形式或F(ab')2片段形式存在的、与二乙烯三胺五乙酸（DTPA）或6 - 对异硫氰酸苄基二乙烯三胺五乙酸（CITCDTPA）偶联的153Sm标记的OC125单克隆抗体在皮下接种表达CA125抗原的卵巢腺癌细胞系（SHIN - 3）的裸鼠体内的药代动力学和生物分布。免疫缀合物的比活度为18.5 - 55.5 MBq/mg，其免疫反应性超过65%。对于153Sm - DTPA - OC125F(ab')2，血清稳定性研究表明50%的金属仍与抗体结合。药代动力学研究显示保留半衰期为25.1小时，血液清除率为0.72 ml/h。生物分布研究表明，在24小时时肿瘤摄取为每克注射活性的4.53%±0.49%（%ID/g），24小时时肿瘤与肝脏及肿瘤与骨骼的比值分别为0.23±0.02和1.54±0.49。对于153Sm - CITCDTPA - OC125F(ab')2，血清稳定性更高（87%的金属仍与抗体结合），保留半衰期为22.25小时，血液清除率为2.23 ml/h。肿瘤靶向性更好（24小时时为8.30%±3.56%ID/g），24小时时肿瘤与肝脏及肿瘤与骨骼的比值分别为1.17±0.36和7.08±3.09。然而，肾脏滞留仍然较高（24小时时为29.76%±9.41%ID/g）。对于完整的IgG，肾脏摄取降低（24小时时为1.41%±0.49%ID/g），但肿瘤摄取低于片段（24小时时为1.46%±0.58%ID/g）。肝脏摄取更高（肿瘤与肝脏比值为0.10±0.05），血液清除更慢。153Sm - CITCDTPA在放射免疫治疗中的稳定性和分布比153Sm - DTPA更有利。使用传统放射自显影和成像板系统获得的数字化图像进行的定量分析表明，后一种系统适用于免疫缀合物的生物分布研究。
