A Novel Method of 18F Radiolabeling for PET
A Novel Method of 18F Radiolabeling for PET
复制标题
DOI：
10.2967/jnumed.108.060418
复制
发表时间：
2009-06-01
影响因子：
9.3
通讯作者：
Goldenberg, David M.
中科院分区：
文献类型：
--
作者：
McBride, William J.;Sharkey, Robert M.;Goldenberg, David M.
小的生物分子通常通过将其与碳原子结合来标记F-18，这一过程通常是为每个新分子独特地设计的，需要几个步骤和几个小时才能生产出来。我们报道了一种简便的方法，其中F-18首先以(Alf)-F-18的形式连接到铝上，然后再结合到与多肽结合的螯合物上，在有效的1-POT过程中形成稳定的(Alf)-F-18-螯合-多肽复合体。方法：为了证明原理，将该方法应用于一种适用于双特异性抗体预靶向方法的多肽。在pH 4.0的醋酸钠缓冲溶液中，AlCl3中心点6H(2)O溶液与F-18水溶液形成(AlF)-F-18络合物。将其加入IMP449(NOTA-p-Bn-CS-D-Ala-D-Lys(HSG)-D-Tyr-D-Lys(HSG)-NH2)的溶液中(NOTA-p-Bn-CS由S-2-(4-异硫氰基苯甲基)-1，4，7-三氮杂环烷-1，4，7-三乙酸制成，HSG为组胺-琥珀酰甘氨酸)，加热至100℃15分钟。以抗CEACAM5双特异性抗体(TF2)为靶点，研究了(Alf)-F-18-IMP 449在荷人结肠癌LS174T裸鼠体内的稳定性和靶向性。结果：以5%-20%的产率合成了放射性多肽，其比活度为18,500-48,100 Gbq(500-1,300 Ci)/mmo1。(Alf)-F-18-IMP 449在体外血清中稳定4h，在动物体内，注射后30min尿液中分离出的活性与其结合。非络合性(Alf)-F-18具有更高的组织摄取率，尤其是在骨骼中，比(Alf)-F-18-IMP 449有更高的组织摄取率，后者通过尿液排泄迅速从体内清除。使用TF2-前靶向(Alf)-F-18-IMP 449的肿瘤摄取率是单独使用多肽的30倍。动态PET显示肿瘤在30min内定位，并迅速彻底清除体内。结论：高度稳定的(Alf)-F-18与金属结合配体的结合能力是一种很有前途的新标记方法，应该适用于不同的PET分子阵列。
Small biomolecules are typically radiolabeled with F-18 by binding it to a carbon atom, a process that usually is designed uniquely for each new molecule and requires several steps and hours to produce. We report a facile method wherein F-18 is first attached to aluminum as (AlF)-F-18, which is then bound to a chelate attached to a peptide, forming a stable (AlF)-F-18-chelate-peptide complex in an efficient 1-pot process. Methods: For proof of principle, this method was applied to a peptide suitable for use in a bispecific antibody pretargeting method. A solution of AlCl3 center dot 6H(2)O in a pH 4.0 sodium-acetate buffer was mixed with an aqueous solution of F-18 to form the (AlF)-F-18 complex. This was added to a solution of IMP 449 (NOTA-p-Bn-CS-D-Ala-D-Lys(HSG)-D-Tyr-D- Lys(HSG)-NH2) (NOTA-p-Bn-CS is made from S-2-(4-isothiocyanatobenzyl)- 1,4,7-triazacyclononane-1,4,7-triacetic acid; HSG is histamine-succinyl-glycine) and heated to 100 degrees C for 15 min. In vitro and in vivo stability and targeting ability of the (AlF)-F-18-IMP 449 were examined in nude mice bearing LS174T human colonic tumors pretargeted with an anti-CEACAM5 bispecific antibody (TF2). Results: The radiolabeled peptide was produced in 5%-20% yield with an estimated specific activity of 18,500-48,100 GBq (500-1,300 Ci)/mmol. The (AlF)-F-18-IMP 449 was stable for 4 h in serum in vitro, and in animals, activity isolated in the urine 30 min after injection was bound to the peptide. Nonchelated (AlF)-F-18 had higher tissue uptake, particularly in the bones, than the chelated (AlF)-F-18-IMP 449, which cleared rapidly from the body by urinary excretion. Tumor uptake was 30-fold higher with TF2-pretargeted (AlF)-F-18-IMP 449 than with the peptide alone. Dynamic PET showed tumor localization within 30 min and rapid and thorough clearance from the body. Conclusion: The ability to bind highly stable (AlF)-F-18 to metal-binding ligands is a promising new labeling method that should be applicable to a diverse array of molecules for PET.