to therapeutics. Molecular imaging reveals biological processes and pro-
vides a means to quantify the processes under physiological conditions.
New probes are being developed to expand the range of biological pro-
cesses that can be studied as well as to improve specificity and better amplify
the cellular signals. One of the goals of current developments is to pro-
vide diagnostics for the identification of the initial stages of diseases to
allow treatment at early stages. Another goal is to combine PET with other
imaging technologies as the resulting synergy should greatly enhance
the capabilities of either technique alone. For example, the simultaneous
measurement by PET and computer tomography should provide detailed
information, not only about the metabolic processes, but also regarding
vascular information.Parkinson’s disease
Parkinson’s disease is the second most common neurodegenerative dis-
ease after Alzheimer’s disease. The first warning sign is development of a
tremor in one arm. As the disease progresses, voluntary movement becomes
slower with some patients experiencing temporary loss of the ability to
move. Currently there are no effective treatments to prevent the progres-
sion of the disease, including the deterioration and death of neurons that
produce the neurotransmitter dopamine. The loss of the dopamine nerve
terminals in the striatum section of the brain is the cause of most of the
motor symptoms. The reason for the damage to the dopamine neurons
is still under active investigation, with many factors proposed, such as
exposure to abnormal proteins, protein aggregation, and oxidative stress.
The disease also kills neurons that produce other neurological compounds
such as norepinephrine, serotonin, and acetylcholine. Linked to the dis-
ease is the formation of Lewy bodies
inside the neurons. Lewy bodies consist
of filaments of the protein α-synuclein,
which is misfolded and forms polymers.
The role of the properly folded α-
synuclein has not been determined
unambiguously.
PET imaging of the brain can be used
to identify the disease (Figure 19.13).
Dopamine is produced in the body from
the amino acid tyrosine. The aromatic
ring L-tyrosine is modified with the
addition of a hydroxyl group into L-dopa
by tyrosine hydroxlase. This reaction is
followed by the production of dopamine
from L-dopa by dopacarboxylase. The
activity of dopamine nerve terminals is418 PART 3 UNDERSTANDING BIOLOGICAL SYSTEMS USING PHYSICAL CHEMISTRY
Figure 19.13Compared to a healthy person (right),
a patient with Parkinson’s disease (left) will have a
deterioration in dopamine-transporter activity, which is
evident in PET scans. Printed with permission from the
University of Pittsburgh Amyloid Imaging Group.