Schuhmacher J, Klivényi G, Matys R, Kirchgebner H, Hauser H, Maier-Borst W, Matzku S
Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg, FRG.
J Nucl Med. 1990 Jun;31(6):1084-93.
Liver uptake of indium-111 (111In) in mice was investigated following administration of 111In-DTPA murine monoclonal antibodies (111In-DTPA-MAbs) labeled by the cyclic anhydride method. Biodistribution of HPLC-purified 111In-DTPA-MAb preparations was checked with a low (0.2 micrograms) and a high (8.0 micrograms) MAb dose. Using Bio Gel P-30 for desalting the MAb-conjugates, 111In uptake in the liver amounted to 8%-9% of the injected dose (ID) and was independent from the MAb dose, the DTPA-to-MAb molar ratio, tumor growth and biologic variability (different MAbs and different strains of mice). Using Sephadex G-25 for desalting, 0.2 micrograms doses from 7 out of 26 preparations showed increased liver accumulation of 111In in non-tumor mice ranging from 15%-25% of ID. Corresponding high doses led to a "normal" value of 8%-9%. Increased liver uptake of the low dose could not be reduced by coadministration of the unconjugated MAb, but was normal after reinjection of "in vivo filtered" material. An inverse intracellular distribution of 111In activity between sediment and supernatant of liver homogenates, following the administration of the low and the high MAb dose, indicated an artifact of the labeling procedure rather than an inherent biological property of labeled MAbs.
采用环状酸酐法标记铟 - 111（¹¹¹In）-二乙三胺五乙酸（DTPA）鼠单克隆抗体（¹¹¹In - DTPA - MAbs）后，研究了小鼠肝脏对¹¹¹In的摄取情况。用低剂量（0.2微克）和高剂量（8.0微克）的单克隆抗体检查了经高效液相色谱（HPLC）纯化的¹¹¹In - DTPA - MAb制剂的生物分布。使用Bio Gel P - 30对单克隆抗体缀合物进行脱盐处理时，肝脏对¹¹¹In的摄取量相当于注射剂量（ID）的8% - 9%，且与单克隆抗体剂量、DTPA与单克隆抗体的摩尔比、肿瘤生长及生物学变异性（不同的单克隆抗体和不同品系的小鼠）无关。使用葡聚糖凝胶G - 25进行脱盐处理时，26份制剂中有7份的0.2微克剂量在非肿瘤小鼠中显示肝脏对¹¹¹In的蓄积增加，范围为ID的15% - 25%。相应的高剂量则导致“正常”值8% - 9%。低剂量时肝脏摄取增加不能通过同时给予未缀合的单克隆抗体而降低，但再次注射“体内过滤”物质后则恢复正常。给予低剂量和高剂量单克隆抗体后，肝脏匀浆沉淀物和上清液中¹¹¹In活性呈反向细胞内分布，这表明是标记过程的假象而非标记单克隆抗体的固有生物学特性。
