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Am J Nucl Med Mol Imaging 2013;3(3):194-216
Review Article
PET radiopharmaceuticals for probing enzymes in the brain
Jason P Holland, Paul Cumming, Neil Vasdev
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard
Medical School, 55 Fruit St., White 427, Boston, MA 02114, USA; Department of Nuclear Medicine, Universitätsklinikum Erlangen,
Ulmenweg 18, Erlangen, Germany, 91054
Received January 6, 2013; Accepted March 7, 2013; Epub April 9, 2013; Published April 15, 2013
Abstract: Biologically important processes in normal brain function and brain disease involve the action of various protein-based
receptors, ion channels, transporters and enzymes. The ability to interrogate the location, abundance and activity of these entities in
vivo using non-invasive molecular imaging can provide unprecedented information about the spatio-temporal dynamics of brain
function. Indeed, positron emission tomography (PET) imaging is transforming our understanding of the central nervous system and
brain disease. Great emphasis has historically been placed on developing radioligands for the non-invasive detection of
neuroreceptors. In contrast, relatively few enzymes have been amenable to examination by PET imaging procedures based upon
trapping or accumulation of enzymatic products, because only a subset of enzymes have sufficient catalytic rate to produce
measureable accumulation within the practical time-limit of PET recordings. However, high affinity inhibitors are now serving as
tracers for enzymes, particularly for measuring the abundance of enzymes mediating intracellular signal transduction in the brain,
which offer a rich diversity of potential targets for drug discovery. The purpose of this review is to summarize well-known radiotracers
for brain enzymes, and draw attention to recent developments in PET radiotracers for imaging signal transduction pathways in the
brain. The review is organized by target class and focuses on structural chemistry of the best-established radiotracers identified in
each class. (ajnmmi1302002).
Keywords: Positron emission tomography, monoamines, second messengers, kinase inhibitors, esterases
Address correspondence to: Dr. Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General
Hospital, and Department of Radiology, Harvard Medical School, 55 Fruit St., White 427, Boston, MA 02114, USA. Phone:
+1-617-643-4736; Fax: +1-617-726-6165; E-mail: vasdev.neil@mgh.harvard.edu
Review Article
PET radiopharmaceuticals for probing enzymes in the brain
Jason P Holland, Paul Cumming, Neil Vasdev
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard
Medical School, 55 Fruit St., White 427, Boston, MA 02114, USA; Department of Nuclear Medicine, Universitätsklinikum Erlangen,
Ulmenweg 18, Erlangen, Germany, 91054
Received January 6, 2013; Accepted March 7, 2013; Epub April 9, 2013; Published April 15, 2013
Abstract: Biologically important processes in normal brain function and brain disease involve the action of various protein-based
receptors, ion channels, transporters and enzymes. The ability to interrogate the location, abundance and activity of these entities in
vivo using non-invasive molecular imaging can provide unprecedented information about the spatio-temporal dynamics of brain
function. Indeed, positron emission tomography (PET) imaging is transforming our understanding of the central nervous system and
brain disease. Great emphasis has historically been placed on developing radioligands for the non-invasive detection of
neuroreceptors. In contrast, relatively few enzymes have been amenable to examination by PET imaging procedures based upon
trapping or accumulation of enzymatic products, because only a subset of enzymes have sufficient catalytic rate to produce
measureable accumulation within the practical time-limit of PET recordings. However, high affinity inhibitors are now serving as
tracers for enzymes, particularly for measuring the abundance of enzymes mediating intracellular signal transduction in the brain,
which offer a rich diversity of potential targets for drug discovery. The purpose of this review is to summarize well-known radiotracers
for brain enzymes, and draw attention to recent developments in PET radiotracers for imaging signal transduction pathways in the
brain. The review is organized by target class and focuses on structural chemistry of the best-established radiotracers identified in
each class. (ajnmmi1302002).
Keywords: Positron emission tomography, monoamines, second messengers, kinase inhibitors, esterases
Address correspondence to: Dr. Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General
Hospital, and Department of Radiology, Harvard Medical School, 55 Fruit St., White 427, Boston, MA 02114, USA. Phone:
+1-617-643-4736; Fax: +1-617-726-6165; E-mail: vasdev.neil@mgh.harvard.edu
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