Camera L, Kinuya S, Garmestani K, Wu C, Brechbiel M W, Pai L H, McMurry T J, Gansow O A, Pastan I, Paik C H
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
J Nucl Med. 1994 May;35(5):882-9.
Serum stability and in vivo biodistribution of both A and B isomers of the 2-(p-isothiocyanatobenzyl) (p-SCN-Bz)-cyclohexyldiethylenetriaminepentaacetic acid ligand (CHX-DTPA), a recently developed backbone-substituted derivative of DTPA, were evaluated and compared to those of 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) and 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetra-acetic acid (2B-DOTA).
Stability of 88Y-labeled ligands (0.1 microM) was evaluated in serum for up to 17 days. For biodistribution, ligands were conjugated to monoclonal antibody (Mab) B3, a murine IgG1k, and labeled with 88Y at 0.1-0.3 mCi/mg. Nontumor-bearing nude mice were injected intravenously with 1-2 microCi/4-10 micrograms of 88Y-labeled B3-conjugates and killed at 6 hr and daily up to 168 hr postinjection. Indium-111-(1B4M)-B3 was co-injected in all mice as internal control.
Serum stability of 88Y-DOTA failed to show any significant release of activity, whereas pseudo-first-order dissociation rate constants of 3.97 x 10(-3), 2.54 x 10(-3) and 1.46 x 10(-2) (day-1) were calculated for 88Y-1B4M, 88Y-CHX-A and 88Y-CHX-B, respectively. Accordingly, cortical bone uptake of 88Y was significantly higher for all DTPA-derivative chelates than for DOTA.
While none of the DTPA-derivative chelates could challenge DOTA in its ability to hold the radioytrium, significant differences were observed in the kinetic inertness of the A and B isomers of CHX, indicating that the CHX-B ligand is not as suitable for 90Y-labeling of Mabs.
对2-(对异硫氰酸苄基)(p-SCN-Bz)-环己基二亚乙基三胺五乙酸配体(CHX-DTPA)（一种最近开发的DTPA主链取代衍生物）的A和B两种异构体的血清稳定性及体内生物分布进行了评估，并与2-(p-SCN-Bz)-6-甲基-DTPA(1B4M-DTPA)和2-(p-SCN-Bz)-1,4,7,10-四氮杂环十二烷四乙酸(2B-DOTA)的血清稳定性及体内生物分布进行了比较。
评估88Y标记配体(0.1 microM)在血清中长达17天的稳定性。对于生物分布，将配体与鼠IgG1k单克隆抗体(Mab) B3偶联，并用88Y以0.1 - 0.3 mCi/mg进行标记。给无瘤裸鼠静脉注射1 - 2微居里/4 - 10微克的88Y标记的B3偶联物，并在注射后6小时及每日直至168小时处死。在所有小鼠中共同注射铟-111-(1B4M)-B3作为内对照。
88Y-DOTA的血清稳定性未显示出任何明显的活性释放，而88Y-1B4M、88Y-CHX-A和88Y-CHX-B的伪一级解离速率常数分别计算为3.97×10(-3)、2.54×10(-3)和1.46×10(-2)（天-1）。因此，所有DTPA衍生物螯合物的88Y在皮质骨中的摄取均显著高于DOTA。
虽然没有一种DTPA衍生物螯合物在保留放射性钇的能力上能与DOTA相抗衡，但观察到CHX的A和B异构体在动力学惰性方面存在显著差异，表明CHX-B配体不太适合用于单克隆抗体的90Y标记。
