Comparison Between [11C]UCB-J and [18F]SynVest-1 PET in HD.

Summary

Positron Emission Tomography (PET) is a functional imaging technique, which enables in vivo visualization of biological molecules expressed in human tissues. Brain PET is most powerful to study a vast range of neurological and psychiatric disorders in vivo, targeting neuronal and glial activity, metabolism, cerebral blood flow, receptor proteins or misfolded proteins.

In vivo imaging of synaptic density in the human brain has become feasible through development of \[11C\]UCB-J, a PET radioligand for the synaptic vesicle protein SV2A, which is ubiquitously and homogeneously present in presynaptic terminals throughout the brain. A first study in Huntington's disease (HD) mutation carriers showed loss of striatal \[11C\]UCB-J binding (also when corrected for atrophy), as well as in the neocortex (Delva et al, Neurology 2022). Moreover, regional synaptic loss was highly correlated to motor impairment.

In order to be able to use SV2A PET as widespread available biomarker tool to assess synaptic integrity, disease progression and/or response to mHTT lowering drugs, the short half-life of 11C (20 minutes) for \[11C\]UCB-J remains a hurdle. Recently, \[18F\]SynVesT-1, an optimized 18F-labeled analogue of \[11C\]UCB-J with similar kinetics, binding affinity, and test-retest precision properties has been evaluated in humans.

However, there is evidence from preclinical studies conducted at University of Antwerp that in the zQ175DN knock-in mouse model of HD, larger variability and lower effect-sizes are seen with \[18F\]SynVest-1 than with \[11C\]UCB-J.

In order to ascertain a similar effect size and quantification properties for \[18F\]SynVest-1 and \[11C\]UCB-J PET in human HD patients and to validate simplified measures (such as SUVR with white matter as reference region) and SynVest, this head-to-head fully quantitative study is performed.

Conditions

• Huntington Disease

Interventions

OTHER

[11C]UCB-J PET

11C-labeled SV2A binding PET radioligand

OTHER

[18F]SynVest-1 PET

18F-labeled SV2A binding PET radioligand

Sponsors & Collaborators

• CHDI Foundation, Inc.

  collaborator OTHER

• Universitaire Ziekenhuizen KU Leuven

  lead OTHER

Principal Investigators

• Koen Van Laere, MD, PhD, DSc · UZ/KU Leuven

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

20 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-11-18

Primary Completion

2026-12-31

Completion

2026-12-31

Countries

• Belgium

Study Locations