Abstract | INTRODUCTION: METHODS: Starting with commercially available 2-nitroimidazole, 2-fluoro-N-(2-(2-nitro-1H-imidazol-1-yl)ethyl)acetamide ( NEFA, [(19)F]7) and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 2-fluoroacetate (NEFT, [(19)F]8), as well as radiolabeling precursors, the bromo-substituted analogs were quickly synthesized through a three-step synthetic pathway. The precursors were radiolabeled with [(18)F]F(-)/18-crown-6/KHCO(3) in dimethyl sulfoxide at 90°C for 10 min followed by purification with an Oasis HLB cartridge. Biodistribution studies were carried out in EMT-6 tumor-bearing mice. The uptake (%ID/g) in tumors and normal tissues were measured at 30 min postinjection. Liquid chromatography-electrospray ionization mass spectrometry (LC/MS) was used to distinguish metabolites from parent drugs in urine and plasma of rat injected with "cold" NEFA ([(19)F]7) and NEFT ([(19)F]8). RESULTS: Two radiotracers, [(18)F] NEFA ([(18)F]7) and [(18)F]NEFT ([(18)F]8), were prepared with average yields of 6%-7% and 9%-10% (not decay corrected). Radiochemical purity for both tracers was >95% as determined by HPLC. Biodistribution studies in EMT-6 tumor-bearing mice indicated that the tumor to blood and tumor to liver ratios of both [(18)F]7 (0.96, 0.61) and [(18)F]8 (0.98, 1.10) at 30 min were higher than those observed for [(18)F] FMISO (1) (0.91, 0.59), a well-investigated azomycin-type hypoxia radiotracer. Liquid chromatography-electrospray ionization mass spectrometry analysis demonstrated that fluoroacetate was the main in vivo metabolite for both NEFA ([(19)F]7) and NEFT ([(19)F]8). CONCLUSIONS: In this research, two new fluorine-18 labeled 2-nitroimidazole derivatives, [(18)F]7 and [(18)F]8, both of which containing in vivo hydrolyzable group, were successfully prepared. Further biological evaluations are warranted to investigate their potential as PET radioligands for imaging tumor.
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Authors | Zhihao Zha, Lin Zhu, Yajing Liu, Fenghua Du, Hongmei Gan, Jinping Qiao, Hank F Kung |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 38
Issue 4
Pg. 501-8
(May 2011)
ISSN: 1872-9614 [Electronic] United States |
PMID | 21531287
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Animals
- Imidazoles
(chemical synthesis, chemistry, pharmacokinetics)
- Isotope Labeling
- Ligands
- Mice
- Neoplasms
(diagnostic imaging, metabolism)
- Positron-Emission Tomography
(methods)
- Rats
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