Assessment of Striatal Dopamine D2/D3 Receptor Availability with PET and ¹⁸F-Desmethoxyfallypride: Comparison of Imaging Protocols Suited for Clinical Routine

Abstract

Assessment of striatal dopamine receptor availability with 18 F-desmethoxyfallypride PET is of high diagnostic utility in parkinsonism. The present study was undertaken to define the optimal clinical scan protocol with regard to quantification accuracy and scan time. Methods: Fourteen patients with parkinsonian syndromes underwent 18 F-desmethoxyfallypride PET over 90 min. Volume-of-interest analyses were performed after spatial normalization, with the right and left caudate nuclei and putamina as target regions and the cerebellum as reference region. The estimate of target region binding potential (relative to nondisplaceable radioligand in tissue) (BP ND ) provided by the 2-step simplified reference tissue model (SRTM2) served as the reference standard. Additional analyses included the multilinear reference tissue model 2 (MRTM2), noninvasive graphical analyses, and single-scan analyses (peak-equilibrium analysis at 35-65 min [PEA]; pseudoequilibrium analysis at 60-90 min [PsEA]). Results: SRTM2 and MRTM2 yielded virtually identical results (mean BP ND difference 5 0.1% 6 0.5%, r 2 5 1.0). Noninvasive graphical analyses with and without inclusion of the k 2 9 term were affected by a small BP ND bias (2.5% 6 3.6% and 25.0% 6 6.7%, respectively), although correlations with SRTM2 were still excellent (r 2 5 1.0 and 0.98, respectively). In turn, singlescan analyses suffered from limited precision (PEA, mean BP ND bias 5 0.7% 6 13.0%, r 2 5 0.90) or a considerable positive bias (PsEA, 19.2% 6 7.1%, r 2 5 0.98). Shortening scan time to 70 and 60 min resulted in an acceptable average BP ND change (,5% decline) for SRTM2/MRTM2 and graphical analysis with inclusion of the k 2 9 term, respectively. Conclusion: Kinetic reference tissue model analyses of 18 F-desmethoxyfallypride PET data offer the least biased results at a well-tolerable scan duration and should thus be pursued whenever possible. Single-scan analyses may be pragmatic alternatives that, however, suffer from a relevant positive bias (PsEA) or limited precision (PEA).

Optimization of the k2′ Parameter Estimation for the Pharmacokinetic Modeling of Dynamic PIB PET Scans Using SRTM2

“…Previous studies using SRTM2 for pharmacokinetic modeling employed different approaches for k ′ 2 estimation. For example, this parameter was evaluated by coupling all target time activity curves for radiotracers designed for D2/D3 receptors [17,18] and radioligands with a high affinity for the serotonin transporter [19]. Tracers such as [ 11 C]P943 [20], used for quantifying serotonin 5-HT1B receptors, use the median value of the k ′ 2 estimation for all voxels that have a BP SRTM ND value between 0.5 and 4, and [ 18 F]DPA-714 [21], used for neuroinflammation, the median of all k ′ 2 values from all voxels in the image.…”