Please note! This essay has been submitted by a student.
In Brain Tumours evaluation, PET is clinically applied after CT or MRI diagnosis. Different pharmaceutical tracers have been proposed for PET imaging of Tumours and their use provide specific advantages, as observed. This table summarizes the spectrum of functions PET imaging can provide when applied to oncology studies and diagnosis. This section will discuss some of these tracers and which information they can delivery.
High protein metabolism and transport in tumours can be accessed to obtain diagnosis. 11C-methionine has been used to access the metabolization of MET, which is necessary in cell proliferation. This tracer is limited by the half-life of 11C, which makes necessary special facilities to its application. Other tracers as 18F-DOPA and 18F-FET are also based on the protein metabolism, but not face the same logistical barriers as 11C-MET. A study comparing 18F-DOPA and 18F-FET in patients with recurrent astrocynoma or glioblastoma were performed. The researchers found that each tracer has specific advantages. While 18F-DOPA delivered a better contrast by having a higher tumour/brain and tumour/blood signal ratios; 18F-FET provides a better information on the tumour grading. This shows how tracers aiming the same process can still be selected to answer a specific question within the brain disease study.
Alzheimer’s disease is a neurodegenerative disease characterized by the deposition of amyloid beta, the presence of neuro tangles, neuronal death and neuroinflammation. The diagnosis of AD was for a long time based on cognitive assays and the confirmation of the disease is obtained at the post-mortem stages, when the presence of amyloid-plaques can be assessed, and the other non-AD dementia can be discarded. The ability of obtained a clear diagnosis, especially at early stages, could improve the knowledge on the disease progression and give more tools to the development of new drugs.
An early study on the sensitivity of PET scan to provide data for dementia diagnosis was performed on a total of 284 patients. The authors performed a longitudinal study with a follow up of at least 2 years to determine the sensitivity of PET to progressive dementia metabolic patterns. For this purpose, the authors conduced PET scan on patients with administration of 2-fluoro-2-deoxy-D-glucose and compare results with cognitive symptoms and the results obtained after autopsy patients. The authors classified the patients depending on the distribution of 2-fluoro-2-deoxy-D-glucose and obtained 93% sensitivity on dementia progression patients. Furthermore, the authors were able to differentiate AD from other neurodegenerative diseases with 94% sensitivity, indicating that PET scan can be an important ally in diagnosis patients.
The developmental of a new tracer called Pittsburgh Compound-B amplified the possibilities of research in AD by using PET. N-methyl-2-6-hydroxybenzothiazole, or PiB, can be used to detect the individual amyloid plaques and be used in AD diagnosis. This was first demonstrated in humans by Klunk et al. In this study, 17 patients were subjected by PET under PiB administration and another time under 18FDG. The results of this study suggest that amyloid deposition analysis in vivo using PET and PiB can be an important tool to characterize AD. Furthermore, this study shows how several aspects can be assessed in the same patient using PET and using for comparison and diagnosis or further investigation on the disease mechanism. The result is showed in Figure 6, the images were using the different tracers were acquire with maximum 30 days interval.
Others AD markers aiming for amyloid plaques were also tested in AD patients and have been compared and use routinely in some centers. Florbetaben was test for sensibility in patients at least 55 years old, from different countries and it was found that 80% of sensibility of this tracer for detecting AD and 91% specificity, which was similar to other studies using the tracer. This high specificity of the tracer allows the differentiation of AD and other Non-AD dementias. Similar results were obtained by using Florbetapir, a similar compound, and the post-mortem evaluation were similar to what was found in the patients during PET analysis. Although both tracers have some limitations, Florbetaben and Flobetapir were approved by FDA to the routinely use in AD diagnosis.
In conclusion, the use of PET and the development of specific markers for amyloid plaques could improve the early diagnosis in patients that are not symptomatic; help to distinguished AD from other dementia that lack amyloid-beta deposition; and be use in the quantification and evaluation of the extension in which these plaques can be found.
Several neurological disorders have in common the development of inflammatory activity in the brain. This neuroinflammation process was found in AD, schizophrenia, Parkinson’s disease, multiple sclerosis, brain tumours and others. Neuroinflammation occur by activation of microglia, which in normal conditions has a reparative function and it has a benefit for the organism in its acute form. When neuroinflammation is prolonged and it is presented in the chronic form, microglia activation causes an extensive destruction of healthy brain tissue and it is associated with the mentioned diseases.
Neuroinflammation has been followed by intravenous injection 11C-(R)-PK11195. Microglia activation can be monitored by the expression of benzodiazepine receptor, or 18k translocator-protein, in mitochondria outer membrane. TSPO expression under normal condition is limited to some areas as the perivascular cells and ependymal layer. PK11195 can bind to this receptor and when it is combined with a 11C isotope, can be used as neuroinflammation marker in PET studies.
Schizophrenia is marked by episodes of delusions hallucinations and disconnection with reality. The knowledge of these episodes is not so well defined and in vivo brain imaging of the biological process could help unravel several related mechanisms. Microglia activation seems to have an important function in schizophrenia and its presence was observed in post-mortem evaluation. One study using 11C-(R)-PK11195 as a tracer found a high correlation of its binding pattern in the hippocampus of patients during psychosis when compared with healthy patient. In the same study, MRI evaluation was performed, and no evidence of brain abnormalities were found using only this technique. This study helps understanding the mechanism behind psychotic events, at the moment they are in course, and gives another tool by follow-up evaluation after specific treatments. This longitudinal evaluation is an advantage of PET over invasive methods and was reported to be done on schizophrenia patients but focusing on a different type of tracer.
PET was combined with a different tracer in schizophrenia called 11C-PBR28, which also binds to TPSO. In this case, the researchers considered that polymorphism in a determined gene could affect the binding potential of the receptor with tracers, generating different profiles in binding affinity. In this study, the researchers were able to show the high binding capacity of the tracer, suggesting activated microglia, in patients classified as ultra-high risk for psychosis and patients with schizophrenia. The later was found even when the data was corrected by genotype differences. This study shows, besides the findings on microglia activation in ultra-risk patients, the different aspects that should be taken into consideration when using a specific tracer in PET studies.
The use of PET in brain imaging seems to be an important tool in the characterization and studies of several different processes. PET in association with MRI can be used in the diagnostic of different neurological diseases and its specific tracers’ targets could improve the differential diagnosis and help distinguishing diseases with similar cognitive outcomes. The continual discovery of new tracers and the investment in technology improvement could give PET an important role in brain research and neurological diseases’ diagnosis.