Positron emission tomography
Positron emission tomography (PET) is a versatile imaging modality that
utilizes radioactive ligands to gauge the integrity of the dopamine
system, cerebral glucose metabolism, pathological Aβ and tau protein
accumulation and neuroinflammation [46].
6‐18F‐fluoro‐L‐dopa (18F-dopa) is a
presynaptic PET tracer that is converted to18F-dopamine by aromatic L-amino acid decarboxylase
(AADC). Thus, 18F-dopa measures the activity of AADC
and provides an indirect estimation of the nigrostriatal dopamine
storage pools.
In line with DAT-SPECT findings, striatal PET imaging of presynaptic
DAT, using for example 18F-FP-CIT or11C-methylphenidate tracers, has found reduced uptake
in the putamen and SN in PD and atypical parkinsonism [46]. As
compared with DAT-PET, DAT-SPECT or AADC-PET, PET imaging of VMAT-2
using 11C-dihydrotetrabenazine
(11C-DTBZ) seems to be less prone to compensatory
changes. Thus, decreased striatal VMAT-2 binding more reliably reflects
the nigrostriatal degeneration in PD. This has been confirmed in
experimental settings, too [52].
Animal models indicate that lesion of locus coeruleus, the main
noradrenergic nucleus in the brain, may be important for the
pathogenesis of non-motor symptoms of PD [53]. PET ligand
(S,S)-11C-2-(α-(2-methoxyphenoxy)benzyl)morpholine
(11C-MeNER) labels noradrenaline transporter, and
several studies in PD patients show reduced noradrenergic innervation in
the brain supporting the view that 11C-MeNER can be
used as one imaging biomarker for non-motor symptoms of PD.
PD causes functional changes in multiple neuronal networks. These
changes are reflected by a specific pattern of abnormal glucose
metabolism in resting-state 18F-fluorodeoxyglucose
(18F-FDG) PET referred to as PD-related pattern
(PDRP), or a distinct PD-related cognitive pattern (PDCP) [54]. PDRP
can be used to discriminate between idiopathic PD, atypical parkinsonian
syndrome and healthy controls. PDRP and PDCP also show promise as
biomarkers to follow the progression of the disease.
PET ligands can be used to assess the degree of neuroinflammation in the
brain [55]. 11C-(R )-PK11195 binds to
mitochondrial translocator protein (formally a peripheral benzodiazepine
receptor), the upregulation of which is indicative of augmented
microglial activation. 11C-(R )-PK11195 uptake
correlates with various aspects of PD pathology in the brain and can be
used in combination with other markers to support the diagnosis.
A major limitation in the development of valid imaging biomarkers for PD
is the incapacity for direct a-syn imaging in vivo . Considerable
efforts are underway to develop a-syn-specific radiotracers for PET
imaging [56]. Such tracer would allow for tracking the degree and
location of a-syn pathology over time and monitoring efficacy of a-syn
targeting therapies.
In addition to CNS imaging also peripheral imaging modalities warrant
attention as the initial pathological a-syn inclusions appear in the
peripheral autonomic and enteric nervous systems even decades prior to
the diagnosis of PD [57]. For example, loss of sympathetic and
parasympathetic nerve terminals can be visualized
using 18F-dopamine and 11C-donepezil
PET imaging, and radiological techniques can reveal dysmotility and
prolonged transit time through the gastrointestinal tract in PD
patients.
Collectively, brain imaging modalities seem to comprise the most
promising biomarker candidates in PD because they provide a direct
approach to measure specific neurofunctional properties and the same
methodology can be applied both to experimental animals and humans
[57]. Even though imaging modalities assure relatively accurate
conclusions, they are expensive, may entail harmful radiation and are
available only in specific centers limiting their usefulness in standard
diagnostics [58]. Thus, they may not be feasible to be used in
screening purposes in large populations. Imaging, however, may prove to
be the most useful approach in confirming the diagnosis triggered by
more accessible screening methods.