PET: Tomografía de Emisión de Positrones

• Técnica de medicina nuclear

• Ciclotrón y cámaras PET/TAC

• Permite cuantificar la cinética de sustancias trazadoras ionizantes

• En tejidos animales o humanos

• Permitiendo medir los procesos fisiológicos y bioquímicos

Ciclotrón •acelerador de partículas

•transforma blancos no radiactivos en nucleidos inestables

• que generan positrones

•ejemplos: 18F, 11C y 15O

Dada la posibilidad de marcar el carbono y el oxígeno, gran parte de las substancias orgánicas existentes pueden ser marcadas y su trayecto dentro del organismo vivo revelado

Emisión de positrones

Electrón

Positron (+)

511 keV

511 keV

FDG

•La fluordeoxiglucosa marcada con 18F es el trazador más utilizado en la PET

•Tiene múltiples indicaciones en oncología y neurologia

•Muchos creen que la FDG es la PET

•El CUDIM aspira a tener una batería de trazadores que nos permita entrar en una etapa más avanzada de la técnica

Tracers11C-Choline Prostata cancer, brain tumors11C- y 18F-Acetate Prostata cancer11C-Methionine Brain tumors, parathyroidea tumors11C- y 18F-Metomidate Adrenocortical carcinomas and adenomas11C-Raclopride D2 Receptors, prolactinoma; Parkinson, Parkinsonismo11C-Flumazenil Epilepsy, neurodegeneration11C-Hydroxytryptophan Neuroendocrin tumors11C-Hydroxiefedrine Pheochromocytoma11C- y 18F-DOPA Presinaptic degeneration : Parkinson, Parkinsonism11C-Deuterodeprenyl Astrocytosis cerebral, CJD, Alzheimer, etc11C- y 18F-PIB Amyloidosis, Alzheimer11C-Nomifensine Parkinson, Parkinsonism11C-Beta-CIT Parkinson, Parkinsonism11C-N-Methylspiperone Parkinson, Parkinsonismo, squizofrenia11C-SCH 23390 Parkinson (D1 receptors)11C-PK11195 Microgliosis18F-FDDPN Amyloidosis and neurofibrillary tangles11C-NST-ML10 Apoptosis in stroke15O Oxígen extraction and y consumtionde15O-CO Cerebral Bood volume15O-H2O Blood Flow

NeurologyDementia: FDG, Deprenyl, PIB

Epilepsy: FDG and Flumazenil

Tumours: Methionine, Raclopride, FDG and Deprenyl

Parkinson’s disease: DOPA, FDG, Raclopride and CIT

Dementia Tracers: FDG, Deprenyl, PIB

To differentiate between:

Alzheimer's disease, Lewy Bodies disease, frontotemporal dementia, multiinfarctions dementia, limbic encephalitis, Creutzfeldt-Jakob’s disease and corticobasal degeneration

Early Diagnosis and follow-up in Alzheimer's disease.

PIB

Cognition

FDG

Diagnosis PIB Diagnosis FDG

Hypothetical steps in the disease progression

Critical pointCritical point

Time (years)

CognitionFDG

PIB

Engler, 2006

•This tracer has good specificity for amyloid deposits in vitro and it seems also to be a promising candidate for application as an in vivo agent of processes related to amyloid plaque formation in man.

Prion diseases

*Sporadic Creutzfeldt-Jakob disease (CJD)

*Familial CJD

*Fatal familial imnsomnia

*Gerstman-Sträussler-Scheinker syndrome

*Iatrogenic CJD

*Variant CJD (bovine spongiform encephalopathy)

Neuropathologic changes

• Neuronal loss

• Astrocytosis

• Spongiform changes

• Deposits of Protease resistent prion protein in brain

* Characterization of astrocytosis

* Characterization of neuronal degeneration

Tracers

[11C]-Deuterodeprenyl (MAO - B binding)

[18F]-FDG (glucose transport)

*FDG and DED showed a typical pattern withdecreased glucose metabolism (cell dysfunction)and increased DED binding (astrocytosis)

Patients with definite and probable CJD

*Frontal, occipital and parietal cortices were the more affected regions

Epilepsy Tracers: FDG and Flumazenil

• Preoperative investigation when MRT, EEG and SPECT have been inconclusive.

• FDG and Flumazenil can be combined to improve sensibility and specificity in the case of suspect foci outside the temporal lobe.

Tumours Tracers: Methionine, Raclopride, FDG, Deprenyl

• To determinate tumour grade in astrocytomas.

• To differenciate between recidive and radiation necrosis

• To localize the best place for biopsy before operation.

• To follow up the treatment of meningeomas.

• To quantify the level of D2-receptors in Prolactinoma before treatment with D2-agonists.

• To control treatment in hypofysis tumours.

• To differenciate between meningeoma and suprasellar adenoma.

11C-methionine

Astrocytoma:PET evaluation

Parkinson’s disease Tracers: DOPA, FDG, Raclopride, CIT

• To differentiate between Parkinson's disease and Multipel System Atrophy.

• To differentiate between different MSA forms:

Striato-Nigral-Degeneration, Olivo-Ponto-Cerebellar Atrophy and Shy-Drager syndrome.

• To differentiate between Parkinson's disease and Dystonia.

• Diagnosis in Huntington’s and Wilson’s disease.

ProgressiveSupranuclear

PalsyOphthalmoplegia

DysphagiaNeck stiffness

MSASND : No repons to L-Dopa treatment

OPCA: Ataxia

SDS: Autonomic dysfunction Orthostatism

Parkinson’s disease

* 15-20% of patients with diagnosis IPD had APD

* In 23 confirmed cases of MSA, 65% responded to levodopa initially, 35% remained partially responsive until death

Hughes et al, J Neurol Neurosurg Psychiatry 1992

Neuropathology

The distinction between IDP and other akinetorigid

extrapyramidal diseases is of prognostic and

therapeutic value

* Characterization of presynaptic degeneration

* Characterization of postsynaptic degeneration

Tracers

L-[11C]-DOPA (dopamine synthesis)[11C]-CIT-FE (dopamine re-uptake)

[11C]-RAC (dopamine receptors)[18F]-FDG (glucose transport)

20001

Engler

Substantia nigraDopaminPresynaptic neuron

Normal

RAC FDGPutamen

Neurodegeneration

D2-r

DOPA/CIT

Engler, 2001

Substantia nigraDopaminPresynaptic neuron

D2-r

Normal

Parkinson’s disease without treatment

RAC FDGPutamen

NeurodegenerationDOPA/CIT

Engler, 2001

Substantia nigraDopaminPresynaptic neuron

D2-r

Normal

Parkinson’s disease after treatment

RAC FDGPutamen

NeurodegenerationDOPA/CIT

Parkinson’s disease without treatment

Engler, 2001

Engler, 2001

Substantia nigraDopaminPresynaptic neuron

D2-r

Normal

Striato-Nigral degeneration

RAC FDGPutamen

NeurodegenerationDOPA/CIT

Parkinson’s disease after treatment

Parkinson’s disease without treatment