Parkinson's Disease
Conditions
Brief summary
AIM: To validate the tracer \[11C\]donepezil for use in the parasympathetic nervous system. MATERIALS AND METHODS: The Investigators will include 7 healthy males aged 45-75 in our study. The participants will receive a careful medical examination, including a neurological examination, as part of the inclusion process. The subjects also have an MRI scan of the brain. PET/CT scans with \[11C\]donepezil are conducted. Six subjects will receive two PET/CT scans - once for the upper abdominal region and once for the head region two evaluate dynamic binding characteristics of the tracer in internal organ. Additionally, one single subject will receive 5 consecutive whole body PET scans to estimate radioactive dosimetry of this tracer. PERSPECTIVES: The study will potentially result in the development of a PET ligand for imaging the parasympathetic nervous system. This will have applications for research in Parkinson's disease, diabetes, heart disease and other disorders, in which the autonomic nervous system is involved
Detailed description
Please see the published paper wherein all details are listed: In vivo imaging of human acetylcholinesterase density in peripheral organs using 11C-donepezil: dosimetry, biodistribution, and kinetic analyses. Gjerløff T, Jakobsen S, Nahimi A, Munk OL, Bender D, Alstrup AK, Vase KH, Hansen SB, Brooks DJ, Borghammer P. J Nucl Med. 2014 Nov;55(11):1818-24.
Interventions
OTHER[11C]donepezil PET
Positron Emission Tomography (PET) imaging of acetylcholinesterase with the ligand \[11C\]donepezil
Sponsors
Lundbeck Foundation
Per Borghammer
Study design
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
MALE
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* male * 45-75 years
Exclusion criteria
* dementia, * psychiatric diseases, * serious medical illness including any type of previous cancer, any drug with known interaction with the autonomic nervous system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution Volume (DV) of [11C]Donepezil - BASELINE | 1 day (One timepoint) | Logan's graphical analysis is used to calculate Distribution Volumes in Volumes of interest in internal organs (salivary gland, heart, liver, stomach, intestines, kidneys). Arterial blood sampling with radio metabolite correction is performed. |
| Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | 1 day (one timepoint) | SUV values were calculated in 7 internal organs. SUV is a unitless ratio. We normalised to injected dose and bodyweight. SUV (organ) = activity concentration (organ; kBq/mL) \* bodyweight (mL) / injected dose (kBq) Note: it is a common assumption when calculating SUV values that bodyweight equals volume, and therefore the unit mL is appropriate. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| [11C]Donepezil PET \[11C\]donepezil is a radiopharmaceutical used with Positron Emission Tomography (PET) imaging. It is evaluated whether the binding in peripheral tissues is in accordance with known distribution of the parasympathetic nervous system
\[11C\]donepezil PET: Positron Emission Tomography (PET) imaging of acetylcholinesterase with the ligand \[11C\]donepezil
7 healthy control subjects were recruited to this study. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | [11C]Donepezil PET |
|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 6.3 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Distribution Volume (DV) of [11C]Donepezil - BASELINE
Logan's graphical analysis is used to calculate Distribution Volumes in Volumes of interest in internal organs (salivary gland, heart, liver, stomach, intestines, kidneys). Arterial blood sampling with radio metabolite correction is performed.
Time frame: 1 day (One timepoint)
Population: In 6 subjects we analysed Volumes of distribution (Vd) and SUV values in internal organs (parotid, submandibular, spleen, stomach, heart, intestine, pancreas). NOTE: In subject number 7 we examined radioactive dose in 23 target organs (dose: microSv/MBq) and calculated the combined effective dose. The Vd and SUV values listed are from 6 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [11C]Donepezil PET | Distribution Volume (DV) of [11C]Donepezil - BASELINE | Vd - Parotid | 18.0 mL | Standard Deviation 3.3 |
| [11C]Donepezil PET | Distribution Volume (DV) of [11C]Donepezil - BASELINE | Vd - Submandibular | 22.1 mL | Standard Deviation 5 |
| [11C]Donepezil PET | Distribution Volume (DV) of [11C]Donepezil - BASELINE | Vd - Spleen | 21.4 mL | Standard Deviation 7.6 |
| [11C]Donepezil PET | Distribution Volume (DV) of [11C]Donepezil - BASELINE | Vd - Stomach | 26.6 mL | Standard Deviation 11.5 |
| [11C]Donepezil PET | Distribution Volume (DV) of [11C]Donepezil - BASELINE | Vd - Heart | 46.8 mL | Standard Deviation 7.8 |
| [11C]Donepezil PET | Distribution Volume (DV) of [11C]Donepezil - BASELINE | Vd - Intestine | 103.9 mL | Standard Deviation 19.5 |
| [11C]Donepezil PET | Distribution Volume (DV) of [11C]Donepezil - BASELINE | Vd - Pancreas | 189.8 mL | Standard Deviation 103.9 |
Primary
Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE
SUV values were calculated in 7 internal organs. SUV is a unitless ratio. We normalised to injected dose and bodyweight. SUV (organ) = activity concentration (organ; kBq/mL) \* bodyweight (mL) / injected dose (kBq) Note: it is a common assumption when calculating SUV values that bodyweight equals volume, and therefore the unit mL is appropriate.
Time frame: 1 day (one timepoint)
Population: In 6 subjects the SUV values in internal organs were calculated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [11C]Donepezil PET | Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | SUV - Parotid | 2.3 Unitless ratio | Standard Deviation 0.5 |
| [11C]Donepezil PET | Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | SUV - Submandibular | 3.9 Unitless ratio | Standard Deviation 1.1 |
| [11C]Donepezil PET | Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | SUV - Spleen | 3.7 Unitless ratio | Standard Deviation 1.4 |
| [11C]Donepezil PET | Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | SUV - Stomach | 4.8 Unitless ratio | Standard Deviation 1.2 |
| [11C]Donepezil PET | Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | SUV - Heart | 7.4 Unitless ratio | Standard Deviation 0.8 |
| [11C]Donepezil PET | Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | SUV - Intestine | 11.7 Unitless ratio | Standard Deviation 2.4 |
| [11C]Donepezil PET | Standard Uptake Value (SUV) of [11C]Donepezil - BASELINE | SUV - Pancreas | 19.1 Unitless ratio | Standard Deviation 4.2 |