Dosimetry of [11C]CHDI-180R and [11C]CHDI-626.
Condition: Huntington Disease
MeSH terms: Huntington Disease
Study type: Observational

Summary: 
      A better understanding of the HD pathogenesis mechanisms may lead to a better understanding
      of disease pathology, progression and development of targeted therapies.

      [11C]CHDI-00485180-R and [11C]CHDI-00485626 are two novel mutant huntingtin aggregate binding
      PET radioligands which have already demonstrated sensitivity to mutant huntingtin load in
      animal models. In the current study, the biodistribution and dosimetry of both these ligands
      will be investigated in young healthy volunteers according to a standard approach, in 3
      subjects (including both genders) per tracer.
    

Detailed description: 
      For both groups, the dynamic whole-body distribution of the respective tracer labelled with
      [11C] will be measured after IV administration of 370 MBq. Two venous catheters, one on each
      arm, will be used for : 1/ the injection of [11C]CHDI-00485180-R or [11C]CHDI-00485626 tracer
      solution and 2/ for venous blood sampling (blood biochemistry and metabolites).

      All images will be acquired using the SIEMENS Truepoint Biograph 40 PET-CT scanner. First, a
      CT scout will be acquired to set the axial field of view (FOV). The axial FOV should extend
      from the top of the head to the middle of the thighs (approximately 6-7 bed positions). Then,
      a low dose CT will be acquired for enabling PET attenuation correction and anatomical
      information (organ delineation). Following the CT, 10 sets of WB 3D PET images in total will
      be acquired sequentially. The first set of 9 whole body PET scans (scan segment 1) will be
      acquired, starting at the time of injecting [11C]CHDI-00485180-R solution or
      [11C]CHDI-00485626 solution. After this sequence of PET acquisitions, which will take up to
      100 min, the subject will be moved out of the scanner and will be encouraged to void the
      bladder. After a 30 minute break, the subject will be repositioned in the PET/CT scanner and
      a second low dose CT will be acquired. WB scan 10 (scan segment 2) will be started at 2 hours
      after [11C]CHDI-00485180-R or [11C]CHDI-00485626 injection, scanning for a total scan
      duration of about 28 minutes.

      During the first WB PET/CT scan segment, 6 venous blood samples (4 mL each) per subject will
      be taken at 5, 10, 20, 40, 60 and 100 min after [11C]CHDI-00485180-R or [11C]CHDI-00485626
      injection. This will allow testing and further optimization of the HPLC metabolite analysis
      for future brain imaging studies with full kinetic modelling and quantification.
    

Intervention name(s): [11C]CHDI-00485180-R; [11C]CHDI-00485626
Intervention type(s): Other; Other
Intervention description(s): Mutant huntingtin aggregate binding PET radioligand.; Mutant huntingtin aggregate binding PET radioligand.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        6 young (18-55 years), healthy subjects, 3 for panel A ([11C]CHDI-00485180-R) and 3 for
        panel B [(11C]CHDI-00485626). Each panel should include both genders (i.e., 2M/1F or
        2F/1M).
      
Biospecimen description: 
      -  2 urine samples for radio-activity assessments (3th sample prior to scanning for female
           participants for pregnancy test)

        -  6 venous blood samples for metabolite analysis
    
Keywords: Positron Emission Tomography