Effect of scan-time shortening on the 11C-PHNO binding potential to dopamine D3 receptor in humans and test–retest reliability

Abstract

Abstract Objective 11C-PHNO is a PET radioligand most specific to dopamine D3 receptor (D3R). The long scan duration of 120 min used in quantification of 11C-PHNO binding to D3R in previous studies is challenging to subjects. The main objective of this study was to investigate the effects of shorter scan times on the binding of 11C-PHNO to D3R and test–retest reliability using the latest digital whole-body PET system. Methods Two 120-min 11C-PHNO brain scans were performed in 7 healthy subjects using a digital whole-body PET/CT. The binding potential relative to non-displaceable tracer in the tissue (BPND) of D3R-rich regions: the pallidum, ventral striatum (VST), substantia nigra (SN) and hypothalamus, were quantified using the simplified reference tissue model. The bias, correlation, and test–retest reliability of BPND, which includes the test–retest variability (TRV) and intraclass correlation coefficient (ICC), were evaluated and compared between scans of shorter durations (40–110 min post-injection) and the original 120-min scan acquisitions. Results Progressively, shorter scan durations were associated with underestimation of BPND, slightly decreased correlation with 120-min derived BPND, and decrease in test–retest reliability. The BPND values of the pallidum, VST and SN from the shortened 90-min scans showed excellent correlation with those derived from the 120-min scans (determination coefficients > 0.98), and the bias within 5%. The test–retest reliability of BPND in these regions derived from 90-min scan (TRV of 3% in the VST and pallidum, 7% in the SN and the ICC exceeded 0.88) was comparable to those obtained in previous 120-min studies using brain-dedicated PET scanners. In the hypothalamus, the BPND values obtained from scan-time less than 110 min showed bias larger than 5% and the TRV more than 9%. Conclusion The scan-time shortening causes bias and decreasing test–retest reliability of 11C-PHNO BPND. However, in the whole-body PET system, 90-min scan duration was sufficient for estimating the 11C-PHNO BPND in the D3R-rich striatum and SN with small bias and at the test–retest reliability comparable to those derived from 120-min scans using the brain-dedicated PET systems.