Impact of scatter correction on D2 receptor occupancy measurements using 123I-IBZM SPECT: Comparison to 11C-Raclopride PET

Reported values of D(2) receptor occupancy (RO) achieved by antipsychotic drugs tend to be lower when measured with (123)I-IBZM SPECT than with (11)C-Raclopride PET. Image degrading factors such as attenuation, distance-dependent collimator response and scatter could account for this difference. While attenuation correction is routinely applied to SPECT images, the other degradations are not usually accounted for. The aim of this work was to assess the impact of scatter correction on D(2) RO quantification with (123)I-IBZM SPECT, and to compare the results of both corrected and un-corrected SPECT values with (11)C-Raclopride PET measurements. Phantom experiments as well as within-subject human data from a previous study were used for this purpose. SPECT images were reconstructed using filtered back-projection including attenuation correction (FBP(A)), ordered subsets expectation maximization including attenuation and point spread function corrections (OSEM(A+PSF)) and ordered subsets expectation maximization including attenuation, point spread function and scatter corrections (OSEM(A+PSF+SCT)). PET images were reconstructed using the FBP algorithm and corrected for attenuation, scatter, random coincidences and dead time. Quantification of receptor availability was performed using the tissue ratio at pseudoequilibrium for SPECT, and the simplified reference tissue model (SRTM) for PET. Analysis was performed using both occipital cortex (occ) and cerebellum (cer) as reference regions for both modalities. When images were reconstructed using FBP(A), SPECT D(2) RO values were significantly lower as compared with PET leading to a D(2) RO difference of -20% (CI(95%): -13, -27%) (occ) and -23% (CI(95%): -14, -31%) (cer). When images were reconstructed using OSEM(A+PSF), SPECT D(2) RO values were also lower as compared with PET leading to a D(2) RO difference of -21% (CI(95%): -14, -27%) (occ) and -24% (CI(95%): -18, -30%) (cer). When images were reconstructed using OSEM(A+PSF+SCT), the D(2) RO bias was reduced to -6% (CI(95%): 0, -13%) (occ) and -11% (CI(95%): -4, -18%) (cer). These data suggest that the scatter correction plays a major role in explaining the differences between D(2) RO measurements using (123)I-IBZM SPECT and (11)C-Raclopride PET.