The purpose of the study is to assess the quantitative accuracy of the experimental HRRT PET scanner and to assess the potential benefits of high resolution PET.
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Data sets obtained with both scanners will be used to derive quantitative PET
pharmacokinetic parameters such volume of distribution and binding potential.
These parameters provide quantitative information about binding of the
administered tracer to the neuroreceptor or about the distribution of
neuroreceptor density. These parameters can be determined at a regional level
using the volumes of interest approach. However, also parametric kinetic
methods will be applied to both datasets in order to derive 3D volumetric
images representing the distribution of the PET pharmacokinetic parameters
across the entire brain at best possible resolution. Parametric analysis will
thus provide quantitative information with highest spatial detail.
Consequently, it will allow most accurate evaluation of PET quantification
improvements with the high resolution PET camera. Finally, by reducing the
resolution of the HRRT scans to that of the clinical HR+ scanner (smoothing) it
is possible to determine whether observed differences in binding potential or
volume of distribution are caused by differences in resolution alone or if
improvements of image reconstruction algorithms or acquisition parameters are
still required.
Secondary outcome
Determination of the quantitative accuracy of the HRRT PET scanner
Background summary
The high-resolution research tomography (HRRT) is a dedicated high resolution
PET scanner designed for human brain imaging. The HRRT is a prototype PET
scanner equipped with depth of interaction to yield a high resolution of ~2.5
full width at half maximum (FWHM) in the entire field of view (scan area). This
resolution is more than a twofold improvement in resolutions of presently
available clinical PET scanners. The higher resolution enables detection and
quantitative assessment of neuroreceptor binding in small brain structures,
such as the hippocampus, which cannot be assessed accurately using the coarser
resolution of a clinical PET scanner (HR+ PET scanner, Siemens/CTI).
Therefore, high resolution PET may become an important tool for evaluation of
neuroreceptor changes for various neurological and psychiatric disorders.
Study objective
The purpose of the study is to assess the quantitative accuracy of the
experimental HRRT PET scanner and to assess the potential benefits of high
resolution PET.
Study design
The performance of the HRRT will be compared with the Siemens HR+ for the use
of neuroreceptor studies. For this purpose three tracers will be used
initially: the D2/D3 receptor tracer [11C]raclopride, the central type
benzodiazepine receptor tracer [11C]flumazenil and the dopamine transporter
tracer [11C]Verapamil. These tracers have been selected because for all these
tracers reference tissue procedures are available for quantification of
specific binding. Use of these tracers therefore allows evaluation of
neuroreceptor PET for both reference and plasma input pharmacokinetic models
thereby including the two most quantitative approaches applied in neuroreceptor
PET imaging.
Study burden and risks
Risks associated with participation in this study are related to 1) radiation
exposure; 2) idiosyncratic reaction to the tracer; 3) placement of intra-venous
and intra-arterial catheters; 4) discomfort during scanning.
1) Radiation exposure
The effective dose equivalent (EDE) of 1 PET study with a bolus injection of
370 MBq [11C]raclopride is 2.5 mSv (Ribeiero, 2005), of 370 MBq [11C]Flumazenil
2.5 mSv and of 370 MBq [11C]Verapamil 2.5 mSv. For comparison, the natural
background radiation dose in the Netherlands gives an annual dose of 2 - 2.5
mSv. Thus, the total radiation exposure of two PET studies with any of these
tracers ( i.e. maximal 5 mSv) is within an acceptable range. In case of
previous exposure to radioactivity, subjects will be eligible if the yearly
cumulative dose due to exposure to radiation remains below 10 mSv.
2) Idiosyncratic reaction to the tracer
The dose of these tracers used in this study is negligible. All these
radiotracers have been used in humans previously. Side effects have never been
reported at the tracer doses used in PET studies.
3) Intravenous and arterial cannulation
There is a very small risk of infection and bleeding associated with
intravenous and arterial cannulation, which are prevented by proper techniques.
4) Discomfort during scanning
It may be uncomfortable to lie motionless in the cameras (both PET and MRI) and
it may cause some subjects to feel anxious. Subjects will be made acquainted
with the surroundings beforehand. Our staff will be available to provide
support, reduce anxiety, optimise the comfort of the subject and remove the
subject from the scanner if requested.
4) Blood sampling.
Adverse effects of blood sampling will be minimized by exclusion of subjects
with low hemoglobin levels (Hb must be > 8 mmol / liter at the time of the scan
for males and be > 7 mmol / liter for females). No more than 500ml blood will
be withdrawn during the total PET procedure and screening. Subjects are
excluded if 3 months before the PET procedure substantial blood loss or a blood
donation has occurred. Subjects are advised not to give blood until 3 months
after the scan has been completed.
de Boelelaan 1117
1081 HV Amsterdam
Nederland
de Boelelaan 1117
1081 HV Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
age between 25 and 70 years
good physical health
RDC diagnosis never mentally ill
BMI between 20-25
scores on Mini mental state examination (MMSE) ><=27
Exclusion criteria
· Any clinical significant abnormality of any clinical laboratory test, including drug screening.
· Any subject who received any investigational medication within 30 days prior to the start of the study or who is scheduled to receive an investigational drug.
· Any major current psychiatric diagnosis on axis-1 of DSM-IV
· History of psychiatric or neurological illness
· History of psychiatric or neurological illness in first-degree relatives
· History of alcohol and/or drug abuse (DSM-IV criteria)
· Current use of any medication
Design
Recruitment
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 |
|---|---|
| CCMO | NL11990.029.06 |