Skip to content
Snippets Groups Projects
Commit 2388e34f authored by Vesa Oikonen's avatar Vesa Oikonen
Browse files

added content; restructuring

parent 1af20e53
No related branches found
No related tags found
No related merge requests found
Pipeline #68719 passed
Stage: test
Stage: deploy
Show whitespace changes
Inline Side-by-side
content/analysis_18f-fdopa.html
+ 71
− 18
View file @ 2388e34f
--- ---
title: Analysis of PET measurements of FDOPA title: Analysis of PET measurements of FDOPA
author: Vesa Oikonen author: Vesa Oikonen
updated_at: 2023-10-30 updated_at: 2023-11-15
created_at: 2009-02-18 created_at: 2009-02-18
tags: tags:
- Dopamine - Dopamine
...@@ -122,16 +122,29 @@ metabolites in the plasma. The main metabolites in plasma are FDA, 3-O-sulphato- ...@@ -122,16 +122,29 @@ metabolites in the plasma. The main metabolites in plasma are FDA, 3-O-sulphato-
<a href="https://doi.org/10.1186/2191-219X-3-18">Tuomela et al., 2013</a>). <a href="https://doi.org/10.1186/2191-219X-3-18">Tuomela et al., 2013</a>).
OMFD can pass the <a href="./blood_brain_barrier.html">blood-brain barrier (BBB)</a> via the same OMFD can pass the <a href="./blood_brain_barrier.html">blood-brain barrier (BBB)</a> via the same
<a href="./transporters_aa.html">amino acid transporters</a> as FDOPA. <a href="./transporters_aa.html">amino acid transporters</a> as FDOPA.
The rate of metabolism and relative proportions of plasma metabolites is affected by enzyme The rate of peripheral metabolism and relative proportions of plasma metabolites is affected by
inhibitors (such as carbidopa) that are commonly administered before FDOPA PET study, or that are enzyme inhibitors (such as carbidopa) that are commonly administered before FDOPA PET study, or
routinely used with L-DOPA medication that are routinely used with L-DOPA medication
(<a href="https://doi.org/10.1186/2191-219X-3-18">Tuomela et al., 2013</a>).</p> (<a href="https://doi.org/10.1186/2191-219X-3-18">Tuomela et al., 2013</a>).
Carbidopa pretreatment increases plasma [<sup>18</sup>F]FDOPA concentration, and consequently the
radioactivity concentration in the brain
(<a href="https://doi.org/10.1016/0024-3205(90)90228-j">Melega et al., 1990</a>), but does not
affect the Patlak plot influx rate
(<a href="https://pubmed.ncbi.nlm.nih.gov/1634937/">Hoffman et al., 1992</a>).
In glioma studies, the carbidopa pretreatment increases SUV in tumour and healthy brain, and
does not affect the tumour-to-healthy-brain ratio
(<a href="https://doi.org/10.3390/cancers13215340">Bros et al., 2021</a>).</p>
<p>Transport of FDOPA and OMFD across BBB is affected by the competition with amino acids in <p>Transport of FDOPA and OMFD across BBB is affected by the competition with amino acids in
the plasma and brain. DOPA is synthesized endogenously in the brain. Under normal physiological the plasma and brain. DOPA is synthesized endogenously in the brain. Under normal physiological
conditions the transport is close to saturation for both influx and efflux conditions the FDOPA transport is close to saturation for both influx and efflux, and
<em>K<sub>1</sub></em> and <em>k<sub>2</sub></em> are approximately inversely proportional to
the concentration of large neutral amino acids in the plasma and brain, respectively
(Cunningham and Lammertsma, 1989). (Cunningham and Lammertsma, 1989).
</p> <a href="https://doi.org/10.1002/ana.410200212">Leenders et al (1986)</a> have shown that
intravenous amino acid loading reduced FDOPA brain uptake about 3-fold compared to the fasting
conditions.</p>
<p>Transport of amino acids from plasma to <a href="./rbc.html">red blood cells</a> is slow. <p>Transport of amino acids from plasma to <a href="./rbc.html">red blood cells</a> is slow.
For L-DOPA the equilibration half-life is &sim;1 h For L-DOPA the equilibration half-life is &sim;1 h
...@@ -150,32 +163,63 @@ the tail of <a href="./organ_pancreas.html">the pancreas</a>.</p> ...@@ -150,32 +163,63 @@ the tail of <a href="./organ_pancreas.html">the pancreas</a>.</p>
<h3>Gjedde-Patlak graphical analysis with arterial plasma input</h3> <h3>Gjedde-Patlak graphical analysis with arterial plasma input</h3>
<p>Reference region (cerebellum or occipital cortex) TAC is first subtracted from the ROI or <p>Multiple-time graphical analysis for irreversible kinetics
image pixel TACs. Applied time range for line fit has been varied in the numerous studies applying (<a href="./model_mtga.html#patlak">Patlak plot</a>) has frequently been used to analyze brain
[<sup>18</sup>F]FDOPA data, but the labelled metabolites of [<sup>18</sup>F]FDOPA must be accounted
for in the analysis. Plasma data must be corrected for labelled metabolites.
Reference region (cerebellum or occipital cortex) TAC is subtracted from the TAC of
region-of-interest (ROI) or TACs of image pixels.
The radioactivity concentration in reference region consists mainly of
[<sup>18</sup>F]FDOPA and [<sup>18</sup>F]OMFD, and after the subtraction the concentration in
region of interest represents the concentration of [<sup>18</sup>F]FDA and its metabolites,
enabling better assessment of AADC activity
(<a href="https://doi.org/10.1002/ana.410260407">Martin et al., 1989</a>).</p>
<p>In regional analysis the rate constant can be calculated per striatum,
mL plasma)&times;(striatum&times;min)<sup>-1</sup>. In this case, striatal ROI is drawn so that it
covers the the whole striatum as visible in the PET image, including any spill-out activity;
the regional radioactivity concentrations (<em>C</em>) and the volumes (<em>V</em>) or areas of
the striatal and reference tissue regions are recorded, and the "specific" striatal radioactivity
(<em>A</em>) is then calculated at each time point as</p>
<a name="striatum"></a>
<div class="eqs">
<script type="math/tex; mode=display">
A_\text{striatum} = C_\text{striatum} \times V_\text{striatum} - C_\text{ref} \times V_\text{striatum}
= ( C_\text{striatum} - C_\text{ref} ) \times V_\text{striatum} \nonumber
</script>
</div>
<p>(<a href="https://doi.org/10.1002/ana.410260407">Martin et al., 1989</a>).
This approach may help to reduce the
<a href="./image_pve.html">partial volume effect</a>, and may be clinically more relevant measure
of nigrostriatal function than the striatal average.
Usually, though, the subtraction is done simply using regional average TACs, providing also the
Patlak net influx rate constant <em>K<sub>i</sub></em> in usual units
(mL plasma)&times;(ml tissue)<sup>-1</sup>&times;min<sup>-1</sup>. Then the ROIs are usually drawn
based on anatomical reference image.</p>
<p>Applied time range for line fit has been varied in the numerous studies applying
the <a href="./model_mtga.html#patlak">Patlak plot</a>. Time range 20-70 min was used by the <a href="./model_mtga.html#patlak">Patlak plot</a>. Time range 20-70 min was used by
<a href="https://doi.org/10.1176/appi.ajp.162.8.1515">Heinz et al (2005)</a>.</p> <a href="https://doi.org/10.1176/appi.ajp.162.8.1515">Heinz et al (2005)</a>.</p>
<p>Because of the near saturation of FDOPA transport, <em>K<sub>1</sub></em> and
<em>k<sub>2</sub></em> are approximately inversely proportional to the concentration of large
neutral amino acids in the plasma and brain, respectively (Cunningham and Lammertsma, 1989).
<a href="https://doi.org/10.1002/ana.410200212">Leenders et al (1986)</a> have shown that
intravenous amino acid loading reduced FDOPA brain uptake about 3-fold compared to the fasting
conditions.</p>
<h3>Graphical analysis with reference tissue input</h3> <h3>Graphical analysis with reference tissue input</h3>
<p>The slope of <a href="./model_mtga.html#patlak_ref">reference tissue MTGA</a> (Patlak plot) is <p>The slope of <a href="./model_mtga.html#patlak_ref">reference tissue MTGA</a> (Patlak plot) is
a function of <em>k<sub>2</sub></em> and <em>k<sub>3</sub></em>:</p> a function of <em>k<sub>2</sub></em> and <em>k<sub>3</sub></em>:</p>
<a name="kref"></a>
<div class="eqs"> <div class="eqs">
<script type="math/tex; mode=display"> <script type="math/tex; mode=display">
{K_{i}^{ref}} = \frac{k_2 \times k_3}{ k_2 + k_3} {K_{i}^{ref}} = \frac{k_2 \times k_3}{ k_2 + k_3} \nonumber
</script> </script>
</div> </div>
<p>The effect of competing amino acids in the brain is cancelled out from <p>The effect of competing amino acids in the brain is cancelled out from
<em>K<sub>i</sub><sup>ref</sup></em> results.</p> <em>K<sub>i</sub><sup>ref</sup></em> results, because the competition affects similarly
the reference region and the region of interest (ROI).</p>
<p>Cerebellum and occipital cortex have been used as reference regions. <p>Cerebellum and occipital cortex have been used as reference regions.
For example, the rate of loss of nigrostriatal dopaminergic neurons in Parkinson's disease For example, the rate of loss of nigrostriatal dopaminergic neurons in Parkinson's disease
...@@ -279,6 +323,11 @@ and [<sup>18</sup>F]DMFP PET study in detoxified alcoholic patients. ...@@ -279,6 +323,11 @@ and [<sup>18</sup>F]DMFP PET study in detoxified alcoholic patients.
<em>Am J Psychiatry</em> 2005; 162(8): 1515-1520. <em>Am J Psychiatry</em> 2005; 162(8): 1515-1520.
doi: <a href="https://doi.org/10.1176/appi.ajp.162.8.1515">10.1176/appi.ajp.162.8.1515</a>.</p> doi: <a href="https://doi.org/10.1176/appi.ajp.162.8.1515">10.1176/appi.ajp.162.8.1515</a>.</p>
<p>Huang SC, Yu DC, Barrio JR, Grafton S, Melega WP, Hoffman JM, Satyamurthy N, Mazziotta JC,
Phelps ME. Kinetics and modeling of L-6-[<sup>18</sup>F]fluoro-dopa in human positron emission
tomographic studies. <em>J Cereb Blood Flow Metab.</em> 1991; 11(6): 898-913.
doi: <a href="https://doi.org/10.1038/jcbfm.1991.155">10.1038/jcbfm.1991.155</a>.</p>
<p>Kienast T, Hariri AR, Schlagenhauf F, Wrase J, Sterzer P, Buchholz HG, Smolka MN, Grunder G, <p>Kienast T, Hariri AR, Schlagenhauf F, Wrase J, Sterzer P, Buchholz HG, Smolka MN, Grunder G,
Cumming P, Kumakura Y, Bartenstein P, Dolan RJ, Heinz A. Dopamine in amygdala gates limbic Cumming P, Kumakura Y, Bartenstein P, Dolan RJ, Heinz A. Dopamine in amygdala gates limbic
processing of aversive stimuli in humans. <em>Nat Neurosci.</em> 2008; 11(12): 1381-1382. processing of aversive stimuli in humans. <em>Nat Neurosci.</em> 2008; 11(12): 1381-1382.
...@@ -301,6 +350,10 @@ Inhibition of L-[<sup>18</sup>F]fluorodopa uptake into human brain by amino acid ...@@ -301,6 +350,10 @@ Inhibition of L-[<sup>18</sup>F]fluorodopa uptake into human brain by amino acid
positron emission tomography. <em>Ann Neurol.</em> 1986; 20: 258-262. positron emission tomography. <em>Ann Neurol.</em> 1986; 20: 258-262.
doi: <a href="https://doi.org/10.1002/ana.410200212">10.1002/ana.410200212</a>.</p> doi: <a href="https://doi.org/10.1002/ana.410200212">10.1002/ana.410200212</a>.</p>
<p>Martin WR, Palmer MR, Patlak CS, Calne DB. Nigrostriatal function in humans studied with positron
emission tomography. <em>Ann Neurol.</em> 1989; 26(4): 535-542.
doi: <a href="https://doi.org/10.1002/ana.410260407">10.1002/ana.410260407</a>.</p>
<p>Misu Y, Goshima Y (eds.): <em>Neurobiology of DOPA as a Neurotransmitter</em>. <p>Misu Y, Goshima Y (eds.): <em>Neurobiology of DOPA as a Neurotransmitter</em>.
CRC Press, 2006. ISBN: 978-0-415-33291-0.</p> CRC Press, 2006. ISBN: 978-0-415-33291-0.</p>
......
0% or .
You are about to add 0 people to the discussion. Proceed with caution.
Please register or to comment