The objective of this project is to assess the applicability of [18F]PK209 for in vivo imaging of the NMDA receptor.
ID
Source
Brief title
Condition
- Other condition
- Neurological disorders NEC
- Schizophrenia and other psychotic disorders
Synonym
Health condition
onderzoek heeft in de toekomst betrekking op bovenstaande aandoeningen, maar wordt uitgevoerd bij gezonde controles
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1) To assess the whole body biodistribution and dosimetry of [18F]PK209
2) To examine the regional brain uptake, metabolites, and test-retest
variability of [18F]PK209
3) To examine the specific binding potential of [18F]PK209 in the brain before
and after ketamine displacement
Secondary outcome
not applicable
Background summary
NMDA receptor (NMDA-R) dysfunction is present in a wide range of neurological
and psychiatric diseases. In the last decade, a major effort in NMDA-R drug
development has focussed on pharmacological modulation of the PCP binding site
of the NMDA-R binding site as treatment for a wide range of neurological and
psychiatric CNS pathologies, including stroke, head trauma, depression,
cognitive disorders and dementias.
In vivo quantification of the NMDA-R using positron emission tomography (PET)
has long been an elusive goal in nuclear medical imaging. A widely
implementable, well validated radiotracer would be a highly valuable tool for
assessing both NMDA-R availability and its etiology in neurodegenerative and
neuropsychiatric diseases. Importantly, links between academia and industry can
be strengthened; A novel PET radiotracer that can target the NMDA receptor
would allow assessment of the binding of CNS drugs, which will be of high
interest for the development of novel pharmaceuticals.
Recently, a new class of PCP ligands were developed at the VUmc, such as
[11C]GMOM and [18F]PK209, which offer the opportunity investigate the NMDA-R
complex in vivo. Radiochemists at the VUmc have succeeded in synthesizing
[18F]PK209 in high yield. The tracer was evaluated as an NMDA-R selective PET
radioligand in mice and rats, and passed key tracer development decision points
in a multitude of experiments.
Study objective
The objective of this project is to assess the applicability of [18F]PK209 for
in vivo imaging of the NMDA receptor.
Study design
The study consists of three sub studies with three groups of healthy subjects
according to the three objectives. 14 men and women are allowed to participate
in this study with the age range from 18 to 70 years old. In the first group
(N=4) the dosimetry of [18F]PK209 will be assessed. In the second group (N=4)
the brain uptake of [18F]PK209 and variability will be assessed, with 2 PET
scans. In the third group (N=6) the specific binding of [18F]PK209 to the NMDA
receptor will be investigated, by comparing the PET scans of the brain before
and after the administration of 0,5 mg/kg S-ketamine.
Study burden and risks
Risks associated with participation in this study are related to radiation
exposure, placement of intra-venous and arterial catheters, blood sampling,
discomfort during scanning, and (in cohort 3 only) adverse events in response
to ketamine administration.
De boelelaan 1117
Amsterdam 1081HV
NL
De boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
1. Signed informed consent prior to any study-mandated procedure.
2. Healthy male and female subjects, 18 to 70 years of age (inclusive). Healthy status is defined by absence of evidence of any active or chronic disease following a physical examination by a trained physician (assistant), and no clinically significant abnormal results in haematology, blood chemistry, and urinalysis.
3. Body mass index (BMI) between 18 and 34 kg/m2 (inclusive), and with a minimum weight of 50 kg.
4. Able to communicate well with the investigator in the Dutch language and able to comply with the study restrictions.
5. Able to lie comfortably in the PET scanner for a period of two hours.
Exclusion criteria
1. Any known factor, condition, or disease that might interfere with study compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
2. Positive test for drugs of abuse at screening or pre-PET.
3. Intake of an investigational medicinal product within 30 days prior to the start of this study.
4. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening.
5. Any condition that may interfere with MRI scanning, e.g. metal objects in or around the body or claustrophobia
6. Pregnant (as tested within 24 hours of the PET scan) or breastfeeding.
7. Inclusion in a research protocol in the past 3 years involving ionizing radiation, which would result in exceeding the ICRP category IIb limit of 10 mSv in addition to natural background radiation.
8. Unacceptable non-pharmacological substances or concomitant medications at baseline. Especially drugs that extend the QT-interval, or (only for cohort 3) drugs that may interact with ketamine (inhibitors of CYP2B6, CYP2C9, CYP3A4) or any other drugs known or likely to affect with study assessments.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001735-36-NL |
| CCMO | NL49180.029.14 |