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Fluoroazomycin arabinoside (FAZA): synthesis, 2 H and 3 H‐labelling and preliminary biological evaluation of a novel 2‐nitroimidazole marker of tissue hypoxia
Author(s) -
Kumar P.,
Stypinski D.,
Xia H.,
McEwan A. J. B.,
Machulla HJ.,
Wiebe L. I.
Publication year - 1999
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199901)42:1<3::aid-jlcr160>3.0.co;2-h
Subject(s) - biodistribution , chemistry , labelling , nitroimidazole , in vivo , radiochemistry , pharmacokinetics , hypoxia (environmental) , chemical synthesis , pet imaging , pharmacology , in vitro , positron emission tomography , biochemistry , nuclear medicine , organic chemistry , oxygen , medicine , microbiology and biotechnology , biology
1‐α‐D‐(5‐Fluoro‐5‐deoxyarabinofuranosyl)‐2‐nitroimidazole (fluoroazomycin arabinoside, FAZA) 6 , a putative PET imaging agent when labelled with 18 F, was synthesized by fluorination of 1‐α‐D‐(2,3‐di‐O‐acetylarabinofuranosyl)‐2‐nitroimidazole 3 with DAST followed by deprotection. The C‐5′‐deuterated and tritiated analogues were prepared by NaCNBD 3 or NaCNBT 3 reduction of the protected C‐5′‐carbonyl intermediate 5 , followed by C‐5′ fluorination and deprotection, to afford C‐5′ deuterated and C‐5′ tritiated FAZA, respectively. Preliminary in vivo biodistribution studies in a murine tumour model, and pharmacokinetic studies in rats indicated that 3 H‐FAZA has biodistribution, tumour uptake and pharmacokinetic properties similar to those of 123 I‐IAZA, a clinically‐proven radiopharmaceutical for SPECT‐imaging of hypoxic tissues. Copyright © 1999 John Wiley & Sons, Ltd.