This document provides an overview of 99mTc TRODAT imaging for Parkinson's disease and other indications. It discusses the nigrostriatal and other dopamine pathways, common ligands used for dopamine imaging including 99mTc TRODAT, patient preparation and acquisition, and interpretation of scans. Key points covered include distinguishing idiopathic Parkinson's disease from vascular parkinsonism using dopamine imaging, and assessing disease severity and progression over time with quantitative analysis of tracer uptake in striatal and extrastriatal regions.
2. Overview
Introduction to Dopamine Imaging
TRO-DA-T
Parkinsonism and other indications
Patient Preparation, Acquisition &
Reconstruction
Interpretation
Review of Literature
5. Introduction to Dopamine Imaging
1 Nigrostriatal Pathway
2 Mesolimbic Pathway
3 Mesocortical Pathway
Motor Function
Motivational behaviour
Cognitive function
7. LIGANDS
AADC [18F]-DOPA
D1 Receptor [11C]-SCH23390
D2 Receptor [11C]-Raclopride [18F]-fallypride [123I]-IBZM
DAT [11C]-CFT [99mTc]-TRODAT [123I]-beta-CIT
VMAT [11C]-DTBZ
MAO A [11C]-clorgyline
MAO B [11C]L-deprenyl
8. Several DAT radio ligands have been examined :
• [11C] cocaine
• three structurally related compounds containing
the tropane moiety:
WIN 35 428 (also known as CFT)
RTI-55 (also known as b-CIT)
TRODAT-1
11. Parkinson’s disease
Attention deficit hyperactivity
disorder
Alcohol hallucinosis
Rubral tremor
Vascular parkinsonism
Machado-Joseph disease
Tourette’s syndrome
Spinocerebellar ataxia
DOPA-responsive dystonia
Manganese intoxication
Carbon disulfide toxicity
Drug-naive schizophrenia
Major depression
Wilson’s disease
Early corticobasal degeneration
Multiple system atrophy
Age and gender differences in DAT
Various pathologies
evaluate with TRODAT 1
in studies
12. Movement disorders:
• Common but heterogeneous group of
disorders.
• PD is the second most common
neurodegenerative disease after AD and most
common hypokinetic movement disorder.
• In majority, clinical diagnosis is not difficult
• Accuracy of clinical diagnosis is generally very
good, but up to 10% to 20% of cases may still
be misdiagnosed.
13. Parkinson Disease:
• Progressive neurodegenerative disorder
• Characterized by a large number of motor (rest
tremor, rigidity, bradykinesia, and gait
impairment, known as the "cardinal features" of
the disease) and non-motor features
• Depending on degree of involvement, variable
impact on function
14.
15.
16. Atypical Parkinson disorders:
Several primary NDDs have in common parkinsonian
features such as bradykinesia, rigidity, tremor, and gait
disturbances.
Conditions that are associated with complex clinical
presentations that reflect degeneration in various neuronal
systems resulting in the term Parkinson plus.
They include
• Multisystem atrophy (MSA)
• Progressive supra-nuclear palsy (PSP)
• Corticobasal degeneration (CBD)
• Dementia with Lewy bodies (DLB)
• PD with amyotrophic lateral sclerosis (ALS)
17. Secondary (acquired ) Parkinsonism:
• Vascular (usually due to striatal lacunar infarcts),
• drug-induced
• viral encephalitis-related parkinsonism
Importantly, they rarely respond to levodopa therapy
18. Clinical staging is the present standard of reference
for following disease progression
Unified Parkinson’s Disease Rating Scale(UPDRS)
UK Parkinson’s Disease Society Brain Bank
National Institute of Neurological Disorders and
Stroke (NINDS)
19. STAGING
Hoehn and Yahr scale (H-Y)
stage 0 (no signs of disease) to
stage 5 (wheelchair bound or bedridden unless assisted)
Scale has a number of distinct limitations
symptoms fluctuate from day to day
Inter observer variability.
Incapable of detecting presymptomatic disease.
20. PD is diagnosed on clinical criteria
No definitive test for diagnosis
Historically, pathological confirmation of the hallmark Lewy body
on autopsy has been considered the criterion standard for
diagnosis
Based on the presence of a combination of
Cardinal motor features,
Associated and exclusionary symptoms, and
Response to levodopa.
21. WHY IMAGING ( IF DIAGNOSIS IS CLINICAL)
Unexpectedly high rate of misdiagnosis if the
diagnosis is based on only the clinical diagnostic
criteria
Loss of approximately 80% dopamine
innervations is needed before symptoms
manifest
Early diagnosis
22. Role of imaging
Differential diagnosis( differentiating PD from other
parkinsonian disorders)
Monitoring disease progression and
Treatment effects
23.
24. • Main indication is striatal DaT visualization in the
evaluation of adult patients with suspected Parkinsonian
Syndromes; to differentiate essential tremor from tremor
due to presynaptic Parkinsonian syndromes
• Early diagnosis of presynaptic Parkinsonian syndromes.
• Differentiation of presynaptic Parkinsonian syndromes
from parkinsonism without presynaptic dopaminergic
loss, such as drug-induced parkinsonism or
psychogenic parkinsonism
• Differentiation of dementia with Lewy bodies from
Alzheimer’s disease
26. Check for medications or drugs that may alter tracer binding, and (if
possible) stop such medication for at least 5 half-lives.
Severely decrease:
--Cocaine, amphetamines, and methylphenidate
--ephedrine and phentermine
May decrease:
--Bupropion, fentanyl, and some anesthetics (ketamine,
phencyclidine, and isoflurane
--1Selective serotonin reuptake inhibitors
Cholinesterase inhibitors and neuroleptics probably do not interfere
significantly with 123I-ioflupane binding to DaT
Anti-Parkinsonian drugs (e.g., L-dihydroxyphenylalanine,
dopamine agonists, monoamine oxidase B inhibitors, N-methyl-D-
aspartate receptor blockers, amantadine, and catechol-O-
methyltransferase inhibitors in standard dosages) do not interfere with
123Iioflupane binding to DaT to any significant degree
30. SEVERITY
(H–Y stage I)
63-y-old female patient
left side tremor and bradykinesia
Decreased significantly in the
right striatum
Slightly reduced in the left
putamen.
31. (H–Y stage III)
B/L bradykinesia,dominant
in the left side
62-y-old female
Uptake decreased
significantly in b/l putamen
Slightly reduced in b/l
caudate nuclei
32. (H–Y stage V)
Decreased uptake in all
defined regions.
63-y-old male patient
Severe bilateral akinesia.
33. IDIOPATHIC PD Vs VASCULAR PARKINSON (VP)
The clinical symptoms of PD and VP may be similar,
but the pathogenesis quite different.
PD VP
PATHOLOGY NEURO-DEGENERATION CHRONIC
SUBCORTICAL
ISCHEMIA
DA NEURONS IN SN DEGENRATED PRESERVED
MOST AFFECTED PUTAMEN WHITE MATTER
INFARCTS