1. ¹Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands
2. ²Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
3. ³Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands

Correspondence: MA Kropholler, Department of Nuclear Medicine & PET Research, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: ma.kropholler@vumc.nl

Received 13 October 2005; Revised 30 November 2005; Accepted 23 January 2006; Published online 1 March 2006.

Abstract

[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 K₁/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 SRTM^pl_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 SRTM^pl_corr performed relatively well. Varying blood volume had no effect on performance. In the clinical evaluation, SRTM^pl_corr and SRTM had the highest correlations with the plasma input model (R²=0.82 and 0.78, respectively). SRTM^pl_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.