Jones-Wilson T M, Deal K A, Anderson C J, McCarthy D W, Kovacs Z, Motekaitis R J, Sherry A D, Martell A E, Welch M J
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Nucl Med Biol. 1998 Aug;25(6):523-30. doi: 10.1016/s0969-8051(98)00017-1.
The use of copper radioisotopes in imaging and therapy applications has created a greater need for bifunctional chelates (BFCs) for complexing copper radioisotopes to biomolecules. It has been demonstrated that the charge and lipophilicity of the Cu-BFC complex has a significant effect on the in vivo behavior of the radiolabeled Cu-BFC-biomolecule conjugate. To evaluate the effects of charge, stability, and macrocyclic backbone size on the biological behavior of 64Cu complexes, a series of macrocyclic 64Cu complexes have been prepared, and the biodistributions of these agents were evaluated in normal Sprague-Dawley rats. Two macrocyclic backbones, dodecane and tetradecane, were evaluated; cyclen, DOTA, and DO2A were dodecane backbone derivatives, and cyclam, TETA, and et-cyclam were tetradecane backbone derivatives. The biodistributions of the 64Cu-labeled complexes correlated with differences in the size of the macrocycle backbone and the formal charge of the complex. All compounds showed uptake and clearance through the liver and kidneys; however, the positively charged 64Cu complexes showed significantly higher uptake in both of these organs than did the negatively charged or neutral complexes. 64Cu-TETA, a negatively charged complex with the tetradecane backbone, had the most efficient clearance by 24 hours' postinjection. These data suggest that negatively charged complexes may have more favorable clearance properties when used as BFCs.
铜放射性同位素在成像和治疗应用中的使用，使得对用于将铜放射性同位素与生物分子络合的双功能螯合剂（BFC）的需求大增。已证明，铜 - BFC络合物的电荷和亲脂性对放射性标记的铜 - BFC - 生物分子共轭物的体内行为有显著影响。为了评估电荷、稳定性和大环主链大小对64Cu络合物生物学行为的影响，已制备了一系列大环64Cu络合物，并在正常的Sprague - Dawley大鼠中评估了这些试剂的生物分布。评估了两种大环主链，十二烷和十四烷；环烯、DOTA和DO2A是十二烷主链衍生物，而环戊二烯、TETA和乙基 - 环戊二烯是十四烷主链衍生物。64Cu标记络合物的生物分布与大环主链大小和络合物形式电荷的差异相关。所有化合物都显示出通过肝脏和肾脏的摄取和清除；然而，带正电荷的64Cu络合物在这两个器官中的摄取明显高于带负电荷或中性的络合物。64Cu - TETA，一种带负电荷的具有十四烷主链的络合物，在注射后24小时具有最有效的清除率。这些数据表明，当用作BFC时，带负电荷的络合物可能具有更有利的清除特性。
