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Quantification of [11C]-TMSX PET studies

Analysis method

Logan plot

Ishiwata et al. (2003b and 2004) have validated the use of graphical analysis (Logan plot) in estimating distribution volume (DV) values for different tissues. Cerebellum was found to be unsuitable as reference region due to high nonspesific binding. Thus an arterial blood curve is always required as input.

Naganawa et al. (2007) suggest using time range 10-40 min for linear fitting in the Logan plot in the brain.

Corrections for input data

A script called TMSX_input.vbs is available for corrections of plasma data. As input it needs upto six files:

  1. Blood file from the online sampler (*.bld, *.alg, *.lis):,
  2. PET image file (*.img or *.v),
  3. count-rate file (*.cr, *.r, *.head or *.dft),
  4. manual plasma sample file (*p.kbq)
  5. fraction file of parent tracer in plasma (*.rat) and
  6. blood-to-plasma fraction file (*bp.rat); this file is optional, and population average can be used instead by giving "None" to scripts instead of the filename.

and as output, the user will receive calibrated and corrected (for decay, delay and metabolites) plasma curve and a file with metabolite TAC. In addition, the script will create post script images where the user can verify how fit of an exponential function into the fraction data succeeded, how delay correction succeeded and how the result curves look like. Dispersion correction is not applied because the effect of dispersion is minimal in case of an 11C labeled tracer.

How to use the script

Before using the script you should verify that you have proper data. For example the parent fraction data should be saved into a text file. The percentages should be within range 0.0-1.0 instead of 0-100 and outliers should be deleted. The file can look for example like this 

3	0.96 
10	0.96 
20	0.89 
30	0.97 
40	0.91 
60	0.76

and it should be named with extension .rat.

Blood/plasma ratio is assumed to be constant during the study, and script can read the ratio from a given file. If study-specific blood-to-plasma ratio is not measured, then an average value 0.676 can be used; average blood-to-plasma ratio was 0.676 ±0.032 (s.d.), n=8 (unpublished results).

You can find a HTA user interface (TMSX_input.hta) on S:\pet-software\bin\windows\ for the script TMSX_input.vbs and either copy and save the .hta file into your own computer or double click to open it from that directory. The names of input and output files should be filled to the form and then the execution button can be pressed. You will receive a message telling when the execution has ended. Please do go through the created PostScript graphs to verify the success of the process!

The plasma curve that you will receive from the script can then be used as such for the graphical analysis.

References:

Heinonen I, Nesterov SV, Liukko K, Kemppainen J, Någren K, Luotolahti M, Virsu P, Oikonen V, Nuutila P, Kujala UM, Kainulainen H, Boushel R, Knuuti J, Kalliokoski KK. Myocardial blood flow and adenosine A2A receptor density in endurance athletes and untrained men. J Physiol. 2008; 586(Pt 21): 5193-5202.

Ishiwata K et al: Preclinical studies on [11C]TMSX for mapping adenosine A2A receptors by positron emission tomography. Ann Nucl Med., 2003; 17(3):205-211.

Ishiwata K et al: Potential of adenosine A2A receptor antagonist [11C]TMSX for myocardial imaging by positron emission tomography: a first human study. Ann Nucl Med., 2003;17(6);457-462.

Ishiwata K et al: Potential of [11C]TMSX for the evaluation of adenosine A2A receptors on the skeletal muscle by positron emission tomography. Nucl Med Biol., 2004; 31:949-956.

Ishiwata K et al: First Visualization of Adenosine A2A Receptors in the Human Brain by Positron Emission Tomography With [11C]TMSX. Synapse, 2005; 55:133-136.

Mizuno M et al: Greater adenosine A2A receptor densities in cardiac and skeletal muscle in endurance-trained men: a [11C]TMSX PET study. Nucl Med Biol., 2005; 32:831-836.

Naganawa M, Kimura Y, Mishina M, Manabe Y, Chihara K, Oda K, Ishii K, Ishiwata K. Quantification of adenosine A2A receptors in the human brain using [11C]TMSX and positron emission tomography. Eur J Nucl Med Mol Imaging 2007; 34: 679–687.


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