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

Sponsor
Universitaire Ziekenhuizen KU Leuven
Study ID
NCT05360082
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
20 Years - 75 Years
Healthy Volunteers
Accepted

Interventions

  • [11C]UCB-J PET — OTHER
    11C-labeled SV2A binding PET radioligand
  • [18F]SynVest-1 PET — OTHER
    18F-labeled SV2A binding PET radioligand

Study Details

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.

Key Dates

First listed
May 4, 2022
Start date
Nov 18, 2024
Status verified
Dec 2024
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
35 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC

Arms

  • Active Comparator: Cohort 1 + 2: healthy controls
    Age -and sex matched to HD patients (to stage 3 HD patients for cohort 1 and to stage 2 HD patients for cohort 2)
  • Experimental: Cohort 1: stage 3 manifest HD patients
    * HTT CAG repeat expansion 40 - 50; * stage 3 as determined by the HD-ISS staging criteria; * UHDRS TFC \>/= 10.
  • Experimental: Cohort 2: stage 2 manifest HD patients
    * HTT CAG repeat expansion 40 - 50; * stage 2 as determined by the HD-ISS criteria; * PIN score 0.47 to 1.84.

Primary Outcome Measure

Compare Vt of [11C]UCB-J and [18F]SynVest-1 in manifest HD and healthy controls [ Time Frame: A first data analysis will be done when all cohort 1 subjects have undergone evaluations. A go-no-go decision will then be made before proceeding with cohort 2. Data analysis of cohort 2 subjects will follow completion of cohort 2. ]

Central Contacts

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