Simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT)
Simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT)
复制标题
DOI：
10.1023/a:1010684101509
复制
发表时间：
2000-03-01
影响因子：
1.6
通讯作者：
Grierson, JR
中科院分区：
文献类型：
--
作者：
Machulla, HJ;Blocher, A;Grierson, JR
[F-18]FLT（3 '-脱氧-3'-[F-18]氟胸苷）是一种示踪剂，特别适合于肿瘤增殖的FET成像，因为在体内缺乏降解。为了促进[F-18]FLT的临床研究，我们研究了两种新的易于获得的前体，2.3 '-脱水胸苷（AThy）和5'-O-（4，4 '-二甲氧基三苯基甲基）-2.3-脱水胸苷（DMTThy），使用亲核[F-18]氟化物引入标记的常用方法。根据底物浓度、反应时间和温度确定放射化学产率。在AThy（10 mg）的情况下，最佳FLT产率为5.3%+/-1.2（130 ℃，30 min）。DMTThy（10 mg）的标记在160 ℃下在10分钟内给出14.3%+/-3.3。从20 GBq [F-18]氟化物的水溶液开始，新方法允许在90分钟内生产1.3 GBq [F-18]FLT，可用于静脉注射。新的标记程序允许[F-18]FLT合成，而无需长时间制备前体，并且具有临床应用所必需的高重现性。
[F-18]FLT (3'-deoxy-3'-[F-18]fluorothymidine) turned out to be a tracer particularly suitable for FET imaging of tumor proliferation because of lacking degradation in vivo. To facilitate clinical studies with [F-18]FLT, we investigated two new easily accessible precursors, 2.3'-anhydrothymidine (AThy) and 5'-O-(4,4'-dimethoxytriphenylmethyl)-2.3-anhydrothymidine (DMTThy), using a common approach for introducing the label with nucleophilic [F-18]fluoride. Radiochemical yields were determined in dependence on substrate concentration, reaction time and temperature. In the case of AThy (10 mg), best FLT yields were 5.3%+/-1.2 (130 degrees C, 30 min). Labeling of DMTThy (10 mg) gave 14.3%+/- 3.3 at 160 degrees C within 10 minutes. Starting with an aqueous solution of 20 GBq [F-18]fluoride the new method allows to produce 1.3 GBq [F-18]FLT within 90 minutes ready for intravenous injection. The new labeling procedures allow [F-18]FLT synthesis without lengthy preparation of the precursor and with high reproducibility mandatory for clinical application.