Effects of Metabolite Correction for Arterial Input Function on Quantitative Receptor Images With 11C-Flumazenil in Clinical Positron Emission Tomography Studies

2004 ◽  
Vol 28 (3) ◽  
pp. 428-435 ◽  
Author(s):  
Hidehiko Okazawa ◽  
Hiroshi Yamauchi ◽  
Kanji Sugimoto ◽  
Yasuhiro Magata ◽  
Takashi Kudo ◽  
...  
2010 ◽  
Vol 31 (1) ◽  
pp. 243-249 ◽  
Author(s):  
Matthew S Milak ◽  
Alin J Severance ◽  
Jaya Prabhakaran ◽  
JS Dileep Kumar ◽  
Vattoly J Majo ◽  
...  

Positron emission tomography studies of 5-hydroxytryptamine (5-HT)1A receptors have hitherto been limited to antagonist radiotracers. Antagonists do not distinguish high/low-affinity conformations of G protein-coupled receptors and are less likely to be sensitive to intrasynaptic serotonin levels. We developed a novel 5-HT1A agonist radiotracer [11C]CUMI-101. This study evaluates the sensitivity of [11C]CUMI-101 binding to increases in intrasynaptic serotonin induced by intravenous citalopram and fenfluramine. Two Papio anubis were scanned, using [11C]CUMI-101 intravenous bolus of 4.5±1.5 mCi. Binding potential (BPF= Bavail/ KD) was measured before ( n=10) and 20 minutes after elevation of intrasynaptic serotonin by intravenous citalopram (2 mg/kg, n=3; 4 mg/kg, n=3) and fenfluramine (2.5 mg/kg, n=3) using a metabolite-corrected arterial input function. Occupancy was also estimated by the Lassen graphical approach. Both citalopram and fenfluramine effects were significant for BPF ( P=0.031, P=0.049, respectively). The Lassen approach estimated 15.0, 30.4, and 23.7% average occupancy after citalopram 2 mg/kg, 4 mg/kg, and fenfluramine 2.5 mg/kg, respectively. [11C]CUMI-101 binding is sensitive to a large increase in intrasynaptic serotonin in response to robust pharmacological challenges. These modest changes in BPF may make it unlikely that this ligand will detect changes in intrasynaptic 5-HT under physiologic conditions; future work will focus on evaluating its utility in measuring the responsiveness of the 5-HT system to pharmacological challenges.


2014 ◽  
Vol 35 (6) ◽  
pp. 666-676 ◽  
Author(s):  
Etienne Croteau ◽  
Eric Poulin ◽  
Sébastien Tremblay ◽  
Véronique Dumulon-Perreault ◽  
Otman Sarrhini ◽  
...  

2012 ◽  
Vol 33 (1) ◽  
pp. 115-121 ◽  
Author(s):  
Yi Su ◽  
Ana M Arbelaez ◽  
Tammie LS Benzinger ◽  
Abraham Z Snyder ◽  
Andrei G Vlassenko ◽  
...  

Positron emission tomography (PET) with 15O-labeled water can provide reliable measurement of cerebral blood flow (CBF). Quantification of CBF requires knowledge of the arterial input function (AIF), which is usually provided by arterial blood sampling. However, arterial sampling is invasive. Moreover, the blood generally is sampled at the wrist, which does not perfectly represent the AIF of the brain, because of the effects of delay and dispersion. We developed and validated a new noninvasive method to obtain the AIF directly by PET imaging of the internal carotid artery in a region of interest (ROI) defined by coregistered high-resolution magnetic resonance angiography. An ROI centered at the petrous portion of the internal carotid artery was defined, and the AIF was estimated simultaneously with whole brain blood flow. The image-derived AIF (IDAIF) method was validated against conventional arterial sampling. The IDAIF generated highly reproducible CBF estimations, generally in good agreement with the conventional technique.


1999 ◽  
Vol 19 (3) ◽  
pp. 278-287 ◽  
Author(s):  
D. J. Doudet ◽  
G. L.-Y. Chan ◽  
S. Jivan ◽  
O. T. DeJesus ◽  
E. G. McGeer ◽  
...  

The effectiveness of 6-[18F]fluoro-L- m-tyrosine (6FMT) to evaluate dopamine presynaptic integrity was compared to that of 6-[18F]fluoro-L-dopa (6FDOPA) in vivo by positron emission tomography (PET). Six normal and six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -lesioned monkeys received 6FDOPA and 6FMT PET scans on separate occasions with identical scanning protocols. Four measures, the rate of uptake of tracer into striatum using either the arterial input function ( Ki) or the activity in the occipital cortex as the input function ( Kc), the rate of loss of striatal radioactivity ( kloss), and an index of “effective turnover” of dopamine ( kloss/ Ki), were obtained for both tracers during extended PET studies. 6-[18F]Fluoro-L- m-tyrosine was as effective as 6FDOPA in separating normals from MPTP-lesioned subjects on the basis of the uptake rate constants Ki and Kc. However, in contrast to 6FDOPA, it was not possible to differentiate the normal from the lesioned animal using kloss or kloss/ Ki for 6FMT. Thus, FMT appears to be a reasonable, highly specific tracer for studying the activity of aromatic dopa decarboxylase enzyme as an index of presynaptic integrity. However, if one is interested in investigating further the metabolic pathway and obtaining an in vivo estimate of the effective turnover of dopamine (after pharmacologic manipulation, for example), 6FDOPA remains the tracer of choice.


Sign in / Sign up

Export Citation Format

Share Document