Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Molecules. 2012 Mar 27;17(4):3774-93. doi: 10.3390/molecules17043774.
We previously reported 18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: 7-(2-[18F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([18F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[18F]fluoro-4-nitro- benzamide ([18F]2). Preliminary biodistribution experiments of both compounds showed s slow clearance rate from excretory tissues which warranted further investigation for tumor imaging with PET. Here we modified [18F]1 and [18F]2 by introducing polar groups such as ester, hydroxyl and carboxyl and developed three additional 18F-18 labeled pyrazolo[1,5-a] pyrimidine derivatives: (3-Cyano-7-(2-[18F]fluoroethylamino)pyrazolo[1,5-a]-pyrimidin-5- yl)methyl acetate ([18F]3), 7-(2-[18F]fluoroethylamino)-5-(hydroxymethyl)pyrazolo[1,5-a]- pyrimidine-3-carbonitrile ([18F]4) and (S)-6-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)-2-(2-[18F]fluoro-4-nitrobenzamido)hexanoic acid ([18F]5). The radiolabeled probes were synthesized by nucleophilic substitution of the corresponding tosylate and nitro precursors with 18F-fluoride. In Vitro studies showed higher uptake of [18F]3 and [18F]4 than that of [18F]5 by S180 tumor cells. In Vivo biodistribution studies in mice bearing S180 tumors showed that the uptake of both [18F]3 and [18F]4 in tumors displayed an increasing trend while the uptake of [18F]5 in tumor decreased through the course of the 120 min study. This significant difference in tumor uptake was also found between [18F]1 and [18F]2. Thus, we compared the biological behavior of the five tracers and reported the tumor uptake kinetic differences between 2-[18F]fluoroethylamino- and 2-[18F]fluoro-4-nitro- benzamidopyrazolo[1,5-a] pyrimidine derivatives.
我们之前报道了 18F 标记的吡唑并[1,5-a]嘧啶衍生物：7-(2-[18F]氟乙基氨基)-5-甲基吡唑并[1,5-a]嘧啶-3-甲腈([18F]1)和 N-(2-(3-氰基-5-甲基吡唑并[1,5-a]嘧啶-7-基氨基)乙基)-2-[18F]氟-4-硝基-苯甲酰胺([18F]2)。这两种化合物的初步生物分布实验表明，它们从排泄组织中的清除率较慢，这需要进一步研究用于 PET 肿瘤成像。在这里，我们通过引入酯、羟基和羧基等极性基团对[18F]1 和 [18F]2 进行了修饰，并开发了另外三种 18F-18 标记的吡唑并[1,5-a]嘧啶衍生物：(3-氰基-7-(2-[18F]氟乙基氨基)吡唑并[1,5-a]-嘧啶-5-基)甲基乙酸酯([18F]3)、7-(2-[18F]氟乙基氨基)-5-(羟甲基)吡唑并[1,5-a]-嘧啶-3-甲腈([18F]4)和(S)-6-(3-氰基-5-甲基吡唑并[1,5-a]嘧啶-7-基氨基)-2-(2-[18F]氟-4-硝基苯甲酰胺基)己酸([18F]5)。放射性标记探针是通过与 18F-氟化物进行亲核取代相应的 tosylate 和 nitro 前体合成的。体外研究表明，S180 肿瘤细胞对[18F]3 和[18F]4 的摄取高于[18F]5。在携带 S180 肿瘤的小鼠体内生物分布研究中，发现[18F]3 和[18F]4 在肿瘤中的摄取呈增加趋势，而[18F]5 在肿瘤中的摄取随着研究过程的进行而降低。在 120 分钟的研究过程中，肿瘤摄取之间也发现了[18F]1 和[18F]2 之间的这种显著差异。因此，我们比较了五种示踪剂的生物学行为，并报告了 2-[18F]氟乙基氨基-和 2-[18F]氟-4-硝基-苯甲酰胺基吡唑并[1,5-a]嘧啶衍生物之间的肿瘤摄取动力学差异。
