Quantification of rheumatoid arthritis [11C]-R-PK11195 PET studies

PK11195 is a selective ligand for the translocator protein (TSPO), formerly known as peripheral benzodiazepine receptor (PBR). 11C-R-PK11195 PET imaging allows noninvasive in vivo imaging and quantification of macrophages in rheumatoid synovitis, and possibly even in subclinical synovitis (van der Laken et al., 2008; Kropholler et al., 2009). Noninvasive visualization of macrophages may be useful both for detecting early synovitis and for monitoring synovitis activity during treatment (van der Laken et al., 2008).

Analysis methods used in literature

Volume of distribution

van der Laken et al. (2008) reported that 1-tissue compartment model with arterial plasma input can be used to estimate regional volume of distribution (VT) of [11C]-R-PK11195 in synovial tissue, and that [11C]-R-PK11195 uptake in synovial tissue was due to binding to PBR receptors on macrophages.

SUV

van der Laken et al. (2008) also found a good correlation between VT and SUV40-60, as well as good correlation between SUV40-60 and macrophage infiltration in synovial tissue. Kropholler et al. (2009) recommended calculating SUV20-40 in clinical use. Therefore, the scanning procedure could be simplified and shortened to a 20-minute static scan of joints of interest. This would make it a method that could be applied in routine clinical practice (van der Laken et al., 2008; Kropholler et al., 2009).

Suggested analysis method for Turku

When plasma curves corrected for radioactive metabolites are available the 1-tissue compartment model fitting of van der Laken et al. (2008) is preferrable choice for analysis method for regional data. To calculate parametric volume of distribution images the Logan graphical analysis may be recommended (imgdv).

For clinical routine analysis, and when plasma curves are not available, the SUV images can be computed, preferrably from 20 to 40 min after injection.

Processing of plasma data in TPC

A script called PK11195_input.vbs is available for corrections of plasma and blood data. As input it needs five 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) and
  5. fraction file of parent tracer in plasma (*.rat).

and as output, the user will receive metabolite corrected plasma file, blood file and file with metabolite TAC. In addition, the script will create PostScript images where the user can verify how fit of a Hill function into the fraction data succeeded, how delay correction succeeded and how the result curves look like.

How to use the script

You can find a HTA user interface (PK11195_input.hta) on S:\pet-software\bin\windows and either copy and save it 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. Do go through the created images to verify the success of the process!


References:

Kropholler MA, Boellaard R, Elzinga EH, van der Laken CJ, Maruyama K, Kloet RW, Voskuyl AE, Dijkmans BA, Lammertsma AA. Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis. Eur. J. Nucl. Med. Mol. Imaging. 2008 Nov 29.

van der Laken CJ, Elzinga EH, Kropholler MA, Molthoff CF, van der Heijden JW, Maruyama K, Boellaard R, Dijkmans BA, Lammertsma AA, Voskuyl AE. Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum. 2008; 58(11): 3350-3355.

Roivainen A, Någren K, Hirvonen J, Oikonen V, Virsu P, Tolvanen T, Rinne J. Whole-body distribution and metabolism of [N-methyl-11C](R)-1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide in man; an imaging agent for in vivo assessment of peripheral benzodiazepine receptor activity with positron emission tomography. Eur. J. Nucl. Med. Mol. Imaging (in press).


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