Deshpande S V, DeNardo S J, Kukis D L, Moi M K, McCall M J, DeNardo G L, Meares C F
Department of Internal Medicine, University of California Davis Medical Center 95816.
J Nucl Med. 1990 Apr;31(4):473-9.
Yttrium-90 (90Y) is a promising radiometal for therapy of cancer due to its high-energy beta emission and a physical half-life of 2.67 days. Bifunctional chelating agents based on DTPA cyclic anhydride or EDTA do not form Y(III) complexes that are stable under physiologic conditions. A new macrocyclic bifunctional chelating agent based on 1,4,7,10-tetraazacylododecane-N,N',N",N"'-tetraacetic acid (DOTA) forms a stable Y(III) complex. It was converted to p-bromoacetamidobenzyl-DOTA (BAD), and conjugated to monoclonal antibody Lym-1 via 2-iminothiolane, either as the free ligand or as the 88Y chelate. Stability studies of Lym-1-2IT-BAD-88Y in human serum in vitro showed no measurable loss of Y(III) from the ligand over a 25-day period. In Raji-tumored mice, tumor uptake was 16.8% of the injected dose per gram of tissue on Day 3. The bone uptake was 2.0, 3.6, and 2.1% injected dose per gram of tissue on Day 1, 3, and 5, respectively. The biodistribution of the control 88Y-citrate demonstrated continuous increase in bone uptake from 13.8% injected dose per gram on Day 1 to 24.9% injected dose per gram on Day 4.
钇-90（90Y）因其高能β发射和2.67天的物理半衰期，是一种很有前景的用于癌症治疗的放射性金属。基于二乙三胺五乙酸环状酸酐或乙二胺四乙酸的双功能螯合剂不能形成在生理条件下稳定的Y（III）配合物。一种基于1,4,7,10-四氮杂环十二烷-N,N',N",N"'-四乙酸（DOTA）的新型大环双功能螯合剂能形成稳定的Y（III）配合物。它被转化为对溴乙酰氨基苄基-DOTA（BAD），并通过2-亚氨基硫杂环戊烷与单克隆抗体Lym-1偶联，既可以作为游离配体，也可以作为88Y螯合物。Lym-1-2IT-BAD-88Y在人血清中的体外稳定性研究表明，在25天内配体中的Y（III）没有可测量的损失。在接种Raji肿瘤的小鼠中，第3天肿瘤摄取量为每克组织注射剂量的16.8%。第1、3和5天，骨摄取量分别为每克组织注射剂量的2.0%、3.6%和2.1%。对照88Y-柠檬酸盐的生物分布显示，骨摄取量从第1天的每克13.8%注射剂量持续增加到第4天的每克24.9%注射剂量。
