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

Keiko Matsunaga; Misato Tonomura; Kohji Abe; Eku Shimosegawa

doi:10.1007/s12149-022-01819-4

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

Ann Nucl Med. 2023 Apr;37(4):227-237. doi: 10.1007/s12149-022-01819-4. Epub 2023 Jan 19.

Authors

Keiko Matsunaga¹, Misato Tonomura^{2

3}, Kohji Abe^{2

3}, Eku Shimosegawa²

Affiliations

¹ Department of Molecular Imaging in Medicine, Graduate School of Medicine, Osaka University, 2-1, Yamadaoka, Suita, Osaka, 565-0871, Japan. matsunaga.keiko.med@osaka-u.ac.jp.
² Department of Molecular Imaging in Medicine, Graduate School of Medicine, Osaka University, 2-1, Yamadaoka, Suita, Osaka, 565-0871, Japan.
³ Shionogi & Co., Ltd, 1-8, Doshomachi 3-Chome, Chuo-ku, Osaka, 541-0045, Japan.

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 (BP_ND) 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 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 ¹¹C-PHNO BP_ND. However, in the whole-body PET system, 90-min scan duration was sufficient for estimating the ¹¹C-PHNO BP_ND 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.

Keywords: 11C-PHNO; Dopamine D3 receptor; PET; Scan-time optimization; Test–retest study.

MeSH terms

Dopamine*
Humans
Positron Emission Tomography Computed Tomography
Positron-Emission Tomography
Receptors, Dopamine D3* / metabolism
Reproducibility of Results

Substances

Dopamine
Receptors, Dopamine D3