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

Background Dopamine-D2 receptor imaging with single-photon emission computed tomography (SPECT) and [ 123 I]IBZM is of great interest for basic and applied neurosciences. However, the use of kinetic analyses for quantification of dynamic [ 123 I]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. Methods Ten movement disorder patients underwent dynamic SPECT (142 min) after single-bolus [ 123 I]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). Results 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%, R 2 > 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%, R 2 = 0.88). NIGA was affected by a negative bias (− 9.1 ± 6.3%, R 2 = 0.75; MRTM2 as reference) or high variability (− 1.2 ± 7.4%, R 2 = 0.71) for analyses without and with inclusion of the k 2 ′-term, respectively. PsEA showed a positive bias and low correlation in comparison with SRTM2/MRTM2 (7.6 ± 10.8%, R 2 = 0.59), which was considerably improved for PEA (− 2.7 ± 7.6%, R 2 = 0.72). MRTM2 provided parametric images with minimal bias suited for voxel-wise statistical analyses. Conclusions MRTM2 and SRTM2 can be reliably applied to dynamic [ 123 I]IBZM SPECT. PEA is a suitable method for clinical routine, while our results discourage the use of PsEA (current clinical standard).