What does this research mean for the field?

A 10 mL white matter reference region for [11C]UCB-J PET imaging optimizes test-retest reliability and increases sensitivity for detecting synaptic density differences between Parkinson's disease patients and healthy controls compared to the standard 2 mL region. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to evaluate an optimized reference region for [ 11 C]UCB-J imaging to improve test-retest reliability and sensitivity in detecting Parkinson's disease.

April 12, 2026Open Access

Optimized reference region and the effect on test-retest reliability and sensitivity to differences between Parkinson’s disease and control groups with 11 CUCB-J

Puntos clave

This research aims to evaluate an optimized reference region for [<sup>11</sup>C]UCB-J imaging to improve test-retest reliability and sensitivity in detecting Parkinson's disease.
Assessed longitudinal test-retest variability in healthy subjects and Parkinson's disease patients.
Evaluated 10 mL as an optimal reference region compared to a previously used small-volume centrum semiovale area.
Measured distribution volume ratio (DVR) of the substantia nigra and caudate in both groups using varied white matter reference regions.
Significantly reduced variability in test-retest measurements using the 10 mL reference region compared to CS2mL.
Found a significant difference in DVR between Parkinson's disease and healthy subjects using 10 mL, with higher effect sizes for both brain regions.
Achieved less than 10% volume of distribution difference from the CS2mL region.

Resumen

11CUCB-J is a radioligand targeting synaptic vesicle glycoprotein 2A, used to image synaptic density. For quantification, a small-volume centrum semiovale area was previously optimized as a 11CUCB-J reference region (CS2mL); however, due to its small volume, its high variability resulted in reduced reliability. Herein, we evaluated an alternative reference region method to assess longitudinal test-retest reliability and detection of Parkinson's disease (PD). For estimating distribution volume ratio (DVR), CS2mL and eleven white matter (WM) reference regions (range: 0.5-200 mL) were generated. Same-day and longitudinal test-retest variability (TRV) were assessed (24 healthy subjects (HS); n = 10 same-day and n = 20 longitudinal scans, range: 7-1028 days). Each reference region was used to evaluate the substantia nigra (SN) and caudate DVRs in HS (n = 25) and PD (n = 20); 10 mL was the optimal reference region volume, yielding 11CUCB-J DVR measurements with reduced variability in TRV (same-day: 10 mL: 1.2 ± 5.7%, same-day: CS2mL: -0.9 ± 9.2% longitudinal: 10 mL: 1.5 ± 7.0%, CS2mL: 1.6 ± 11.9%), while maintaining d 0.61 for SN and 0.66 for caudate) compared to CS2mL (0.38 for SN and 0.43 for caudate).

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