18F-labeled Pyrazolo[1,5-a]pyrimidine Derivatives: Synthesis from 2,4-Dinitrobenzamide and Tosylate Precursors and Comparative Biological Evaluation for Tumor Imaging with Positron Emission Tomography

Molecules

Jingli Xu¹  Hang Liu¹  Guixia Li¹  Yong He¹  Rui Ding¹  Xiao Wang¹  Man Feng¹  Shuting Zhang¹  Yurong Chen¹  Shilei Li¹  Mingxia Zhao¹  Yingruo Li¹  Chuanmin Qi¹ 

[1] Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China

关键词: ¹⁸F-labeled;    pyrazolo[1;    5-a]pyrimidine derivatives;    2;    4-dinitrobenzamide and tosylate precursors;    PET imaging agents;    tumor detection;   

DOI  :  10.3390/molecules17043774

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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