| Title |
|
|
|
In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat
| |
| Author |
|
|
|
| |
| Abstract |
|
|
|
| [(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. | | |
| Language |
|
|
|
English
| |
| Source (journal) |
|
|
|
European journal of nuclear medicine and molecular imaging. - Heidelberg | |
| Publication |
|
|
|
Heidelberg : 2009
| |
| ISSN |
|
|
|
1619-7070
| |
| Volume/pages |
|
|
|
36:6(2009), p. 958-965
| |
| ISI |
|
|
|
000265940500010
| |
| Full text (Publisher's DOI) |
|
|
| | |
| Full text (publisher's version - intranet only) |
|
|
| | |
|