Effect of scan-time shortening on the (11)C-PHNO binding potential to dopamine D(3) receptor in humans and test–retest reliability

OBJECTIVE: (11)C-PHNO is a PET radioligand most specific to dopamine D(3) receptor (D(3)R). The long scan duration of 120 min used in quantification of (11)C-PHNO binding to D(3)R 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 (11)C-PHNO to D(3)R and test–retest reliability using the latest digital whole-body PET system. METHODS: Two 120-min (11)C-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 (BP(ND)) of D(3)R-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 BP(ND), 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 BP(ND), slightly decreased correlation with 120-min derived BP(ND), and decrease in test–retest reliability. The BP(ND) 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 BP(ND) 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 BP(ND) 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 (11)C-PHNO BP(ND). However, in the whole-body PET system, 90-min scan duration was sufficient for estimating the (11)C-PHNO BP(ND) in the D(3)R-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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12149-022-01819-4.