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Title
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In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat
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Author
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Abstract
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| [(11)C]Flumazenil shows promise as a clinical and research PET radiotracer to image changes in GABA(A) central benzodiazepine receptor (cBZR), but its widespread use has been limited by practical limitations of [(11)C]. This study evaluated the imaging characteristics of two fluorinated PET radiotracers in rats in vivo: [(18)F]fluoroflumazenil ([(18)F]FFMZ) and [(18)F]flumazenil ([(18)F]FMZ). PET acquisitions were performed on a small-animal scanner following injection of [(18)F]FFMZ in nine rats and [(18)F]FMZ in eight rats. The following treatments were investigated: (1) injection of the tracer dose, (2) presaturation then injection of the tracer dose, and (3) injection of the tracer dose followed by a displacement injection. Unchanged tracer was measured in plasma and brain structures in four animals 10 and 30 min after injection, and ex-vivo autoradiography was also performed. For both [(18)F]FFMZ and [(18)F]FMZ maximal brain activity peaked rapidly, and was highest in the hippocampus (1.12 +/- 0.06 SUV, 1.24 +/- 0.10 SUV, respectively), and lowest in the pons (1.00 +/- 0.07 SUV, 1.03 +/- 0.09 SUV, respectively). By 50 min after injection, maximal uptake for [(18)F]FFMZ and [(18)F]FMZ had decreased in the hippocampus to 18 +/- 3% and 80 +/- 1% (p < 0.01), respectively. The presaturation and displacement studies showed a higher nonspecific component for [(18)F]FFMZ than for [(18)F]FMZ. Metabolite studies showed that at 30 min only 10% of the signal was from [(18)F]FFMZ in the brain. This nonspecific binding was apparent on autoradiography. In contrast, [(18)F]FMZ accounted for > 70% of the signal in the brain, which resulted in well-defined regional binding on autoradiography. These results demonstrate that [(18)F]FMZ is a superior radiotracer to [(18)F]FFMZ for in-vivo PET imaging of the GABA(A)/cBZR, having slower metabolism and leading to lower concentrations of metabolites in the brain that results in a substantially better signal-to-noise ratio. |
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Language
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English
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Source (journal)
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European journal of nuclear medicine and molecular imaging. - Heidelberg
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Publication
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Heidelberg
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2009
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ISSN
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1619-7070
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Volume/pages
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36
:6
(2009)
, p. 958-965
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ISI
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000265940500010
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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