Carrasquillo J A, White J D, Paik C H, Raubitschek A, Le N, Rotman M, Brechbiel M W, Gansow O A, Top L E, Perentesis P, Reynolds J C, Nelson D L, Waldmann T A
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
J Nucl Med. 1999 Feb;40(2):268-76.
Monoclonal antibodies (MoAb) labeled with 90Y are being used for radioimmunotherapy. Because 90Y is a beta emitter, quantitative information from imaging is suboptimal. With the concept of a "matched pair" of isotopes, 111In is used as a surrogate markerfor90Y. We evaluated the differences in biodistribution between 111In- and 90Y-labeled murine antiTac MoAb directed against the IL-2Ralpha receptor.
The antiTac was conjugated to the 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid (1B4M-DTPA, also known as MX-DTPA). Nine patients with adult T-cell leukemia were treated. Patients received approximately 185 MBq (5 mCi) 111In-labeled antiTac for imaging and 185-555 MBq (5-15 mCi) 90Y-labeled antiTac for therapy. The immunoreactivity of 111In-labeled antiTac was 90%+/-6%, whereas for 90Y-labeled antiTac, it was 74%+/-12%.
The differences in blood and plasma kinetics of the two isotopes were small. The area undemeath the blood radioactivity curve was 1.91 percentage+/-0.58 percentage injected dose (%ID) x h/mL for 111In and 1.86%+/-0.64 %ID x h/mL for 90Y. Urinary excretion of 90Y was significantly greater than that of 111In in the first 24 h (P = 0.001), but later, the excretion of 111In was significantly greater (P = 0.001 to P = 0.04). Core biopsies of bone marrow showed a mean of 0.0029+/-0.0012 %ID/g for 111In, whereas the 90Y concentration was 0.0049+/-0.0021 %ID/g. Analyses of activity bound to circulating cells showed concentrations of 500-30,000 molecules of antiTac per cell. When cell-bound activity was corrected for immunoreactive fraction, the ratio of 111In to 90Y in circulating cells was 1.11+/-0.17. Three biopsies of tumor-involved skin showed ratios of 111In to 90Y of 0.7, 0.9 and 1.1.
This study shows that differences typically ranging from 10% to 15% exist in the biodistribution between 111In- and 90Y-labeled antiTac. Thus, it appears that 111In can be used as a surrogate marker for 90Y when labeling antiTac with the 1 B4M chelate, although underestimates of the bone marrow radiation dose should be anticipated.
用90钇标记的单克隆抗体（MoAb）正用于放射免疫治疗。由于90钇是β发射体，成像的定量信息欠佳。基于“同位素匹配对”的概念，铟-111用作90钇的替代标志物。我们评估了针对白细胞介素-2受体α链的铟-111和90钇标记的鼠抗Tac单克隆抗体在生物分布上的差异。
将抗Tac与2-（4-异硫氰酸苄基）-6-甲基二乙三胺五乙酸（1B4M-DTPA，也称为MX-DTPA）偶联。对9例成人T细胞白血病患者进行治疗。患者接受约185兆贝可（5毫居里）铟-111标记的抗Tac用于成像，以及185 - 555兆贝可（5 - 15毫居里）90钇标记的抗Tac用于治疗。铟-111标记的抗Tac的免疫反应性为90%±6%，而90钇标记的抗Tac为74%±12%。
两种同位素在血液和血浆动力学方面的差异较小。铟-111的血放射性曲线下面积为1.91%±0.58%注射剂量（%ID）×小时/毫升，90钇为1.86%±0.64%ID×小时/毫升。在最初24小时内，90钇的尿排泄显著高于铟-111（P = 0.001），但之后，铟-111的排泄显著增加（P = 0.001至P = 0.04）。骨髓核心活检显示铟-111的平均值为0.0029±0.0012%ID/克，而90钇浓度为0.0049±0.0021%ID/克。对循环细胞结合活性的分析显示，每个细胞抗Tac的浓度为500 - 30000个分子。当对细胞结合活性进行免疫反应分数校正后，循环细胞中铟-111与90钇的比值为1.11±0.17。对肿瘤累及皮肤的三次活检显示铟-111与90钇的比值分别为0.7、0.9和1.1。
本研究表明，铟-111和90钇标记的抗Tac在生物分布上通常存在10%至15%的差异。因此，在用1B4M螯合物标记抗Tac时，铟-111似乎可作为90钇的替代标志物，不过预计会低估骨髓辐射剂量。
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