Kinuya S, Jeong J M, Garmestani K, Saga T, Camera L, Brechbiel M W, Gansow O A, Carrasquillo J A, Neumann R D, Paik C H
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Nucl Med. 1994 Nov;35(11):1851-7.
The effect of a chelator structure on the metabolic fate of the 111In-labeled monoclonal antibody (Mab) T101 was investigated in normal Balb/c mice to assess the importance of this chemical parameter in the reduction of the background radioactivity in blood and liver.
Mab T101 was conjugated with either 2-(p-isothiocyanatobenzyl)-6-methyl-diethylaminetriaminepentaac etic acid (DTPA) (1B4M), 2-(p-isothiocyanatobenzyl) cyclohexyl-DTPA (CHX-B) or cyclic DTPA dianhydride (cDTPA) and then radiolabeled with 111In. Normal mice were injected intravenously with these 111In-labeled T101 conjugates and sacrificed in groups of five up to 5 days postinjection for comparative biodistribution studies and analyses of liver, blood and urine samples for radioindium products.
The biodistribution of 111In-1B4M-T101 and 111In-CHX-B-T101 were similar to each other but significantly different from that of 111In-cDTPA-T101, particularly in the blood and liver. Size-exclusion high-performance liquid chromatography indicated that the concentration of the intact 111In-immunoglobulin (Ig)G in liver decreased with similar rates for the three conjugates. Meanwhile, the concentration of a small DTPA-like metabolite in liver increased to a different peak value (4.6% ID/g for the cDTPA conjugate and 1.6% ID/g for the 1B4M and CHX-B conjugates) approximately at 24 hr and maintained a steady-state concentration up to 5 days.
The thiourea linkage between T101 and the 111In-labeled chelates and a higher complex stability and higher lipophilicity of 111In-1B4M and 111In-CHX-B appear to be responsible for lower liver and higher blood radioactivity for the 1B4M and CHX-B conjugates.
在正常Balb/c小鼠中研究了螯合剂结构对111铟标记的单克隆抗体（Mab）T101代谢命运的影响，以评估该化学参数在降低血液和肝脏中背景放射性方面的重要性。
将Mab T101与2-（对异硫氰酸苄基）-6-甲基二乙三胺五乙酸（DTPA）（1B4M）、2-（对异硫氰酸苄基）环己基-DTPA（CHX-B）或环DTPA二酐（cDTPA）偶联，然后用111铟进行放射性标记。正常小鼠静脉注射这些111铟标记的T101偶联物，并在注射后5天内按每组5只处死，用于比较生物分布研究以及分析肝脏、血液和尿液样本中的放射性铟产物。
111铟-1B4M-T101和111铟-CHX-B-T101的生物分布彼此相似，但与111铟-cDTPA-T101的生物分布显著不同，尤其是在血液和肝脏中。尺寸排阻高效液相色谱表明，三种偶联物在肝脏中完整的111铟-免疫球蛋白（Ig）G浓度以相似的速率下降。同时，肝脏中一种类似DTPA的小代谢物浓度在大约24小时时增加到不同的峰值（cDTPA偶联物为4.6%注射剂量/克，1B4M和CHX-B偶联物为1.6%注射剂量/克），并在长达5天的时间内保持稳态浓度。
T101与111铟标记的螯合物之间的硫脲键以及111铟-1B4M和111铟-CHX-B更高的络合物稳定性和更高的亲脂性似乎是1B4M和CHX-B偶联物肝脏放射性较低和血液放射性较高的原因。
