This study will investigate the use of [11C]NNC-112 in positron emission tomography (PET)
scanning. PET is a technique that uses radioactive isotopes called tracers to provide images
of the brain. Injected into the body, the isotopes lose their "radioactive strength" over
time, sending out rays that can be picked up and "seen" by special detectors connected to a
computer. The computer then makes a picture of the brain. This study will examine the
distribution in the body of a new tracer called [11C]NNC-112.
Healthy normal volunteers between 18 and 70 years of age may be eligible for this study.
Candidates are screened with a physical examination and blood and urine tests, including a
urine drug screen. Women up to age 55 also have a pregnancy test.
Participants have a PET scan using the [11C]NNC-112 tracer. For this procedure, a catheter
(small plastic tube) is placed into a vein in the subject's arm for injecting the tracer.
Then, the subject lies on the scanner bed. After a preliminary "transmission scan," the
tracer is injected, and PET scans are taken from the head to the upper thigh over a period
of about 2 hours to show the distribution of radioactivity in the body. Blood pressure,
breathing rate, and heart rate are checked before and after injection of the tracer, and
blood and urine samples are collected after the PET scan.
Abnormalities in dopaminergic neurotransmission have been implicated in several
neurodegenerative and psychiatric disorders, such as Parkinson's disease, schizophrenia,
attention-deficit-hyperactivity disorder and drug dependence. Among the Dopamine (DA)
receptors, D1 receptors are understood to be involved in the regulation of motor and
cognitive activity by modulating DAergic function. Neuroreceptor imaging with Positron
Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT) allows
in vivo quantification of the density and distribution of D1 receptors in humans. Recently,
a new and superior PET radioligand for in vivo quantification of D1 receptors in
extrastriatal regions has been developed. [11C]NNC-112 is a D1 radiotracer with high
specific to nonspecific binding, making it suitable for imaging low density D1 receptors in
extrastriatal regions such as the neocortex. Several studies in humans have confirmed the
potential of this radiotracer, however, to date, dosimetry studies of [11C]NNC-112 in humans
have not been performed.
The specific objective of this protocol is to estimate radiation-absorbed doses of
[11C]NNC-112 in human subjects. For this purpose, we propose to perform a kinetic whole body
imaging study of [11C]NNC-112 in healthy human subjects. We hypothesize that the level of
radiation-absorbed doses of [11C]NNC-112 in humans will be within limits, and consequently,
we should be able to move to the next stage of our imaging research, where we will use this
radioligand to measure the density and distribution of D1 receptors in Parkinson's disease.
All subjects must be healthy and aged 18-70 years.
Current psychiatric disease, substance abuse or severe systemic disease based on history
and physical exam
Laboratory tests with clinically significant abnormalities
More than moderate hypertension
Any prior participation in other research protocols within the past year that involve
radiation, with the exception of plain radiography studies (i.e., chest x-rays).
Pregnancy and Breast Feeding
Positive HIV test