PET Imaging

  • Created by: LBCW0502
  • Created on: 18-10-18 14:43
What is a neurological disorder?
Any disorder of the body's nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms (over 600 recorded disorders)
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Previously, what was the best way to make a positive diagnosis?
By performing an autopsy
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Describe features of screening
Laboratory screening - blood, urine, other substances. Neurological exams - motor functions, reflexes, speech coordination and mental status. X-rays - chest and skull
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Describe features of modern diagnosis
Able to view structure and function. Diagnosis of many complex conditions. MRI, fMRI, CT, SPECT, PET, multi-modality imaging, SPECT-CT, PET-CT, PET-MR
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What are the advantages of SPECT and PET? (1)
CT/MRI give structure rather than functional information. Structure rarely altered in psychiatric illness (only occasionally in neurodegenerative disorders). Functions disturbances occur before structural changes so early detection possible
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What are the advantages of SPECT and PET? (2)
In vivo, non-invasive, 3D images may be combined with other modalities
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What are the additional benefits?
Proof of principle - identification of pathophysiology and drug action. Accurate, objective diagnosis. Monitoring of treatment - early identification. Drug research - speed up process (some drug companies have set up PET centres)
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What does PET stand for?
Positron Emission Tomography
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What does positron mean?
Positively charged electron, produced dual photons (single photon - gamma ray) after annihilation
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What is emission?
Emitted on radioactive decay
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What is tomography?
Slice, 3D image
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What does SPECt stand for?
Single Photon Emission Computed Tomography
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What does MR stand for?
Magnetic Resonance
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State features of designated brain PET scanners
Only the head placed in scanner, not the whole body (more difficult to locate e.g. drug)
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Describe features of radiopharmaceuticals
Radiolabelled drugs used for nuclear medicine procedures
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What are the properties of radiopharmaceuticals
Very small chemical quantity administered (pharmacological effects rare). Pharmaceutical quality (most given IV). Radiation dose at acceptable level
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What is the main challenge when using radiopharmaceuticals?
Logistics of preparation to pharmaceutical standard within half-life
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Describe features of neuroreceptors
Proteins on cellular membranes interact with specific ligands to cause distinct response, characterised by affinity and density. Receptors involved in physiological functions (e.g. memory, emotion, pain, motor response).
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Describe features of radioligands being used in neuroreceptor studies
Radioligands used to visualise an quantify the distribution density and activity of the neuroreceptors. Isotopes used, short half life desirable, need rapid synthesis
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Give examples of radionuclides used in SPECT which have a long half-life
Tc- 99m (6h) and I-123 (13h)
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Give examples of radionuclides used in PET which a short half-life
O-15 (2 min), C-11 (20 min) and F-8 (110 min)
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Describe features of designing a radioligand (1)
C/I commonly used due to short half life but isotopes with a longer half-life may be more appropriate to systems with slower kinetics. PET has higher sensitivity but SPECT allows simultaneous trace systems using isotopes emitting different energies
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Describe features of designing a radioligand (2)
Nanomolar affinity and highly selective to receptor, low non-specific binding in brain tissue, rapid permeation in BBB, metabolites avoided in BBB, high specific activity prevent competing reaction from cold ligand
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Outline the concepts of receptor binding studies
Drug with receptor forms complex (equilibrium constants involved). Receptor binding curves, binding potential, parameters in receptor modelling
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Give examples of binding systems which radioligands target?
Dopamine (D1, D2, dopamine transporter), 5HT1A and 5HT2A (serotonin)
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Outline the application of radioligands on the dopamine system
Dopamine has central role in brain functions. Dopamine secretions leads to pleasant feeling/strong rewards system (involved in addictions). Degenerative nigro-striatal dopamine system leads to PD and multi system atrophy (target D1/2 receptors)
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Give an example of a radioligand which high affinity
11C-N-methylspiperone - Butyrophenone neuroleptic (virtually irreversible)
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Give an example of a radioligand which a low affinity
11C-raclopride - Benzamide neuroleptic (dopamine competes, widely used to monitor endogenous dopamine levels)
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Describe features of research application for the role of dopamine in addiction
Factors in addiction: social/behavioural/biological, genetic. Dopamine involved in reward. End stage addiction (cellular adaptations which decrease reward/cognitive control). PET used understand addiction
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Describe features of imaging strategy
11C-Raclopride is a medium affinity ligand for the dopamine D2 receptor (competes with dopamine). Methylphenidate binds to the dopamine transporter (challenge agent, blocks uptake of dopamine, increases dopamine/bind to receptor, displace raclopride)
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Where else can PET imaging be applied to?
Understanding enhanced striatal dopamine release during food stimulation in binge eating disorder
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Describe features of Parkinson's disease
Symptoms include shaking/tremor, stiffness/rigidity, frozen facial expressions. Usually begins unilaterally and progresses to bilateral with increase in severity of symptoms. On/off phenomenon. Can include dementia. Issues with diagnosis
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Describe features of an essential tremor
Benign ET/familial ET. Most obvious when upper limbs in use (rather than at rest). Can be difficult to distinguish from PD. Different treatment used
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Outline the mechanism for the dopaminergic neuron
Tyrosine-TH-DOPA-AADC- Dopamine. DAT involved. Potential effector linkers - cAMP, PI/phospholipase C, K/Ca channel, arachidonic acid
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Describe features of DAT as marker of PD
PD loss of presynaptic neurons. Decrease DAR, decrease DA neuron, lower binding to DAT is indicative of PD
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Describe features of I-Ioflupane-123
Cocaine analogue, binds to DAT, differentiate diagnosis between ET and PD, differential diagnosis of Lewy body dementia
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Describe features of Alzheimer's disease
Neurodegenerative disease characterised by formation of b-amyloid plaques and neurofibrillary tangles. Associated with progressive memory loss and impaired judgement/reasoning. Difficult to diagnose early. Differentiation from multi-infarct dementia
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Which agents are used in PET for Alzheimer's disease?
PET amyloid agents, F-Florbetapir-18, C-PIB-11 (monitor antibodies). F-DOPA-18
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Describe features of drug development
New drugs take 10-12 years to get to market (most do not make it - poor efficacy at maximum tolerated dose/toxicity). PET provides info about kinetics distribution and dosing. Direct - radiolabels (test drug). Indirect - challenge of existing ligand
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Summarise points about PET, SPECT, PD and AD
PEt/SPECT provide non-invasive quantitative measures of neuroreceptor status/function. Used in clinical test measures for DAT in PD. Imaging b-amyloid plaque in AD (huge potential market)
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Card 2

Front

Previously, what was the best way to make a positive diagnosis?

Back

By performing an autopsy

Card 3

Front

Describe features of screening

Back

Preview of the front of card 3

Card 4

Front

Describe features of modern diagnosis

Back

Preview of the front of card 4

Card 5

Front

What are the advantages of SPECT and PET? (1)

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