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The methodology of TSPO imaging with positron emission tomography.

Turkheimer FE, Rizzo G, Bloomfield PS, Howes O, Zanotti-Fregonara P, Bertoldo A, Veronese M - Biochem. Soc. Trans. (2015)

Bottom Line: The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions.However, such major investment has not yet resulted in the expected improvement in image quality.We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Psychiatry, King's College London, London SE5 8AF, U.K. federico.turkheimer@kcl.ac.uk.

No MeSH data available.


Schematic representation of a standard dynamic PET studyThe PET instrumentation allows the quantification of the concentration of the radiotracer in the organ of interest whereas additional instrumentation is used to quantify radioactive concentrations in blood. The latter is then corrected for those tracer fractions bound to red cells, platelets, plasma proteins etc., to recover the free tracer concentration in plasma. The plasma used as input function for the mathematical model that is applied to the data to obtain the parameters of interest. Kinetics curves refer to a representative [11C]-PBR28 PET study in healthy HAB.
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Figure 1: Schematic representation of a standard dynamic PET studyThe PET instrumentation allows the quantification of the concentration of the radiotracer in the organ of interest whereas additional instrumentation is used to quantify radioactive concentrations in blood. The latter is then corrected for those tracer fractions bound to red cells, platelets, plasma proteins etc., to recover the free tracer concentration in plasma. The plasma used as input function for the mathematical model that is applied to the data to obtain the parameters of interest. Kinetics curves refer to a representative [11C]-PBR28 PET study in healthy HAB.

Mentions: Figure 1 illustrates a typical dynamic PET acquisition where, after injection, radioactivity in blood and in the organ of interest is monitored throughout the experiment generally lasting an hour or more. Once the study is completed, the coincident detections of the γ-rays are reconstructed into a set of time frames that measure the distribution of the radioligand during the acquisition. At the same time, the blood data are corrected for radioactive impurities (radioactive metabolites, radioactivity in blood cells and platelets, plasma protein bound fractions) to obtain the concentration of the free tracer in plasma. The availability of absolute measures of the ligand in tissue and plasma, the latter being a very good approximation of the concentration in the capillaries, allows the calculation of functional measures such as blood flow, enzymatic rates and protein densities via a kinetic model.


The methodology of TSPO imaging with positron emission tomography.

Turkheimer FE, Rizzo G, Bloomfield PS, Howes O, Zanotti-Fregonara P, Bertoldo A, Veronese M - Biochem. Soc. Trans. (2015)

Schematic representation of a standard dynamic PET studyThe PET instrumentation allows the quantification of the concentration of the radiotracer in the organ of interest whereas additional instrumentation is used to quantify radioactive concentrations in blood. The latter is then corrected for those tracer fractions bound to red cells, platelets, plasma proteins etc., to recover the free tracer concentration in plasma. The plasma used as input function for the mathematical model that is applied to the data to obtain the parameters of interest. Kinetics curves refer to a representative [11C]-PBR28 PET study in healthy HAB.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4613512&req=5

Figure 1: Schematic representation of a standard dynamic PET studyThe PET instrumentation allows the quantification of the concentration of the radiotracer in the organ of interest whereas additional instrumentation is used to quantify radioactive concentrations in blood. The latter is then corrected for those tracer fractions bound to red cells, platelets, plasma proteins etc., to recover the free tracer concentration in plasma. The plasma used as input function for the mathematical model that is applied to the data to obtain the parameters of interest. Kinetics curves refer to a representative [11C]-PBR28 PET study in healthy HAB.
Mentions: Figure 1 illustrates a typical dynamic PET acquisition where, after injection, radioactivity in blood and in the organ of interest is monitored throughout the experiment generally lasting an hour or more. Once the study is completed, the coincident detections of the γ-rays are reconstructed into a set of time frames that measure the distribution of the radioligand during the acquisition. At the same time, the blood data are corrected for radioactive impurities (radioactive metabolites, radioactivity in blood cells and platelets, plasma protein bound fractions) to obtain the concentration of the free tracer in plasma. The availability of absolute measures of the ligand in tissue and plasma, the latter being a very good approximation of the concentration in the capillaries, allows the calculation of functional measures such as blood flow, enzymatic rates and protein densities via a kinetic model.

Bottom Line: The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions.However, such major investment has not yet resulted in the expected improvement in image quality.We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers.

View Article: PubMed Central - PubMed

Affiliation: Institute of Psychiatry, King's College London, London SE5 8AF, U.K. federico.turkheimer@kcl.ac.uk.

No MeSH data available.