Kinetic analyses of [123I]IBZM SPECT for quantification of striatal dopamine D2 receptor binding: A critical evaluation of the single-scan approach

Dopamine-D2 receptor imaging with single-photon emission computed tomography (SPECT) and [123I]IBZM is of great interest for basic and applied neurosciences. However, the use of kinetic analyses for quantification of dynamic [123I]IBZM SPECT and the validity of the commonly employed single-scan pseudo-equilibrium analysis (PsEA) have not been appropriately investigated. The present study addresses these shortcomings. Ten movement disorder patients underwent dynamic SPECT (142 min) after single-bolus [123I]IBZM injection. Kinetic analyses comprise: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2) and non-invasive graphical analysis (NIGA). Simplified single-scan analyses were performed at peak time of specific binding (peak-equilibrium analysis, PEA) and during pseudo-equilibrium (PsEA). SRTM and MRTM are compromised by the high noise level of dynamic SPECT. SRTM2 and MRTM2 yielded reliable binding potential estimates that agreed excellently (mean difference=−0.1±1.0%, R2>0.99). Concordance between SRTM/MRTM and SRTM2/MRTM2 was high in cases in which SRTM/MRTM provided reliable results (SRTM2 or MRTM2 vs. SRTM: 3.7±5.0%, R2=0.88). NIGA was affected by a negative bias (−9.1±6.3%, R2=0.75; MRTM2 as reference) or high variability (−1.2±7.4%, R2=0.71) for analyses without and with inclusion of the k2′-term, respectively. PsEA showed a positive bias and low correlation in comparison with SRTM2/MRTM2 (7.6±10.8%, R2=0.59), which was considerably improved for PEA (−2.7±7.6%, R2=0.72). MRTM2 provided parametric images with minimal bias suited for voxel-wise statistical analyses. MRTM2 and SRTM2 can be reliably applied to dynamic [123I]IBZM SPECT. PEA is a suitable method for clinical routine, while our results discourage the use of PsEA (current clinical standard).