Evaluation of reference tissue models for the analysis of [ 11C](R)-PK11195 studies

Marc A. Kropholler, Ronald Boellaard, Alie Schuitemaker, Hedy Folkersma, Bart N M Van Berckel, Adriaan A. Lammertsma

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[11C](R)-PK11195 is a marker of activated microglia, which can be used to measure inflammation in neurologic disorders. The purpose of the present study was to define the optimal reference tissue model based on a comparison with a validated plasma input model and using clinical studies and Monte Carlo simulations. Accuracy and reproducibility of reference tissue models were evaluated using Monte Carlo simulations. The effects of noise and variation in specific binding, nonspecific binding and blood volume were evaluated. Dynamic positron emission tomography scans were performed on 13 subjects, and radioactivity in arterial blood was monitored online. In addition, blood samples were taken to generate a metabolite corrected plasma input function. Both a (validated) two-tissue reversible compartment model with K 1/k2 fixed to whole cortex and various reference tissue models were fitted to the data. Finally, a simplified reference tissue model (SRTM) corrected for nonspecific binding using plasma input data (SRTM pl_corr) was investigated. Correlations between reference tissue models (including SRTMpl_corr) and the plasma input model were calculated. Monte Carlo simulations indicated that low-specific binding results in decreased accuracy and reproducibility. In this respect, the SRTM and SRTMpl_corr performed relatively well. Varying blood volume had no effect on performance. In the clinical evaluation, SRTMpl_corr and SRTM had the highest correlations with the plasma input model (R 2=0.82 and 0.78, respectively). SRTMpl_corr is optimal when an arterial plasma input curve is available. Simplified reference tissue model is the best alternative when no plasma input is available.

Original languageEnglish
Pages (from-to)1431-1441
Number of pages11
JournalJournal of cerebral blood flow and metabolism
Issue number11
Publication statusPublished - 15 Nov 2006


  • Microglia
  • PET (positron emission tomography)
  • PK11195
  • Peripheral benzodiazepine receptor
  • Reference tissue models
  • Tracer kinetic modelling

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