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Tesi etd-07242018-113131


Thesis type
Tesi di specializzazione (5 anni)
Author
GENNARO, MARTA
URN
etd-07242018-113131
Title
11C-PBR28 PET to assess the level of brain microglia activation in Huntington's Disease patients
Struttura
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Corso di studi
MEDICINA NUCLEARE
Commissione
relatore Prof. Volterrani, Duccio
relatore Prof.ssa Piccini, Paola
Parole chiave
  • 11C-PBR28
  • microglia activation
  • PET
  • Huntington disease
Data inizio appello
03/09/2018;
Consultabilità
parziale
Data di rilascio
03/09/2021
Riassunto analitico
Background: Huntington disease (HD) is a degenerative inherited disorder, characterized by a progressive motor and cognitive decline. Several studies, both post mortem and in vivo, have demonstrated the role of activated microglia in HD, suggesting that the release of neurotoxins may cause neuronal damage and contribute to the progression of the pathology. The translocator protein 18KDa (TSPO) is overexpressed on the outer mitochondrial membrane of microglia activated and represents a target for PET radioligands, making possible studying in vivo the state of cell activation. 11C-PBR28 is a second generation TSPO radioligand with a favourable kinetic and great signal-to-noise ratio, but with a heterogeneous inter-subjects affinity. Method: 18 HD patients and 10 healthy controls (HC) underwent a dynamic PET scan with 11C-PBR28 and a T1 weighted MRI scan. The TSPO affinity has been evaluated and all subjects were classified as High (HABs) and Middle (MABs) binders according to their genotype. The distribution volume ratio (DVR) of 11C-PBR28 in the striatum was calculated with a ROI based approach using the Logan kinetic model and the occipital lobe as a reference region. Results: HD patients showed a striatal increase in TSPO expression compared with controls. DVR was higher in the striatum of HABs HD compared with HC with the same genotype (p<0.02.) Similar values were detected both in putamen and caudate of MABs HD (p<0.02). No correlations have been found between gender and age and DVR in HD patients. Conclusion: the 11C-PBR28 PET represents a valuable, non-invasive means to detect the state of microglia activation in HD patients. Therefore, it could be used not only to monitor the progression of the disease but also to assess the efficacy of potential therapeutics which modulate the state of neuroinflammation.
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