synthesis and biological evaluation of pyrazolo[1,5-a]-pyrimidine-containing 99mtc nitrido radiopharmaceuticals as imaging agents for tumors合成和生物评价pyrazolo[1 5]-pyrimidine-containing 99矿渣mtc nitrido放射性药物作为肿瘤显像剂.pdfVIP

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synthesis and biological evaluation of pyrazolo[1,5-a]-pyrimidine-containing 99mtc nitrido radiopharmaceuticals as imaging agents for tumors合成和生物评价pyrazolo[1 5]-pyrimidine-containing 99矿渣mtc nitrido放射性药物作为肿瘤显像剂.pdf

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synthesis and biological evaluation of pyrazolo[1,5-a]-pyrimidine-containing 99mtc nitrido radiopharmaceuticals as imaging agents for tumors合成和生物评价pyrazolo[1 5]-pyrimidine-containing 99矿渣mtc nitrido放射性药物作为肿瘤显像剂

Molecules 2010, 15, 8723-8733; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Biological Evaluation of Pyrazolo[1,5-a]-pyrimidine-containing 99mTc Nitrido Radiopharmaceuticals as Imaging Agents for Tumors Rui Ding, Yong He, Jingli Xu, Hang Liu, Xiao Wang, Man Feng, Chuanmin Qi * and Junbo Zhang Key Laboratory of Radiopharmaceuticals, College of Chemistry, Beijing Normal University, Beijing 100875, China; E-Mails: dingrui@ (R.D.); heyong@ (Y.H.); xujingli@ (J.X.); liuhang@ (H.L.); wangxiao@ (X.W.); fengman@ (M.F.); zhjunbo@(J.Z.). * Author to whom correspondence should be addressed; E-Mail: qicmin@; Tel.: +86-136-8138-0097; Fax: +86-010-5880-2075. Received: 1 November 2010; in revised form: 15 November 2010 / Accepted: 24 November 2010 / Published: 30 November 2010 Abstract: The compound 5-((2-aminoethylamino)methyl)-7-(4-bromoanilino)-3-cyano- pyrazolo[1,5-a]pyrimidine (ABCPP) was synthesized and conjugated with N-mercapto- acetylglycine (MAG), N-mercaptoacetylphenylalanine (MAF) and N-mercaptoacetylvaline (MAA), respectively. These three compounds were labeled successfully with [99mTcN]2+ intermediate in high radiochemical purities. Biodistribution in tumor-bearing mice demonstrated that the three new complexes showed tumor accumulation, high tumor-to- muscle (T/M) ratios and fast clearance from blood and muscle. Among them, the 99mTcN- MAG-ABCPP showed the most favorable characteristics, with tumor/bl