title: 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.
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.
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Xu
authors.forename: Hang
authors.initials: H
authors.lastname: Liu
authors.forename: Guixia
authors.initials: G
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Feng
authors.forename: Shuting
authors.initials: S
authors.lastname: Zhang
authors.forename: Yurong
authors.initials: Y
authors.lastname: Chen
authors.forename: Shilei
authors.initials: S
authors.lastname: Li
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhao
authors.forename: Yingruo
authors.initials: Y
authors.lastname: Li
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Qi
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Dang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D012510:Sarcoma 180 / Q000000981:diagnostic imaging* / Q000378:metabolism
chemical_list: D001549:Benzamides; D005462:Fluorine Radioisotopes; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; C527752:pyrazolo(1,5-a)pyrimidine