Molecules 2012, 17(4), 3774-3793; doi:10.3390/molecules17043774
Article

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

Jingli Xu 1 , Hang Liu 1 , Guixia Li 1 , Yong He 1 , Rui Ding 1 , Xiao Wang 1 , Man Feng 1 , Shuting Zhang 1 , Yurong Chen 1 , Shilei Li 1 , Mingxia Zhao 1 , Yingruo Li 1 , Chuanmin Qi 1,* email and Yonghong Dang 2
1 Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China 2 Department of Nuclear Medicine, PUMC Hospital, Beijing 100730, China
* Author to whom correspondence should be addressed.
Received: 22 February 2012; in revised form: 14 March 2012 / Accepted: 19 March 2012 / Published: 27 March 2012
(This article belongs to the Section Medicinal Chemistry)
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Abstract: 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.
Keywords: 18F-labeled; pyrazolo[1,5-a]pyrimidine derivatives; 2,4-dinitrobenzamide and tosylate precursors; PET imaging agents; tumor detection

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Cite This Article

MDPI and ACS Style

Xu, J.; Liu, H.; Li, G.; He, Y.; Ding, R.; Wang, X.; Feng, M.; Zhang, S.; Chen, Y.; Li, S.; Zhao, M.; Li, Y.; Qi, C.; Dang, Y. 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 2012, 17, 3774-3793.

AMA Style

Xu J, Liu H, Li G, He Y, Ding R, Wang X, Feng M, Zhang S, Chen Y, Li S, Zhao M, Li Y, Qi C, Dang Y. 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. 2012; 17(4):3774-3793.

Chicago/Turabian Style

Xu, Jingli; Liu, Hang; Li, Guixia; He, Yong; Ding, Rui; Wang, Xiao; Feng, Man; Zhang, Shuting; Chen, Yurong; Li, Shilei; Zhao, Mingxia; Li, Yingruo; Qi, Chuanmin; Dang, Yonghong. 2012. "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 17, no. 4: 3774-3793.

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