11C- and 18F-Radiotracers for In Vivo Imaging of the Dopamine System: Past, Present and Future

The applications of positron emission tomography (PET) imaging to study brain biochemistry, and in particular the aspects of dopamine neurotransmission, have grown significantly over the 40 years since the first successful in vivo imaging studies in humans. In vivo PET imaging of dopaminergic functions of the central nervous system (CNS) including dopamine synthesis, vesicular storage, synaptic release and receptor binding, and reuptake processes, are now routinely used for studies in neurology, psychiatry, drug abuse and addiction, and drug development. Underlying these advances in PET imaging has been the development of the unique radiotracers labeled with positron-emitting radionuclides such as carbon-11 and fluorine-18. This review focuses on a selection of the more accepted and utilized PET radiotracers currently available, with a look at their past, present and future.

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PET Metabolic Biomarkers for Cancer

Biomarkers in Cancer ◽

10.4137/bic.s27483 ◽

2016 ◽

Vol 8s2 ◽

pp. BIC.S27483 ◽

Cited By ~ 6

Author(s):

Etienne Croteau ◽

Jennifer M. Renaud ◽

Marie Anne Richard ◽

Terrence D. Ruddy ◽

François Bénard ◽

...

Keyword(s):

Pet Imaging ◽

Ketone Bodies ◽

Imaging Biomarkers ◽

Substrate Consumption ◽

Cancer Proliferation ◽

Positron Emission ◽

Pet Radiotracers ◽

Metabolic Biomarkers

The body's main fuel sources are fats, carbohydrates (glucose), proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET) imaging using the glucose analog 18F-fluorodeoxyglucose (18F-FDG) has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

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In VivoPET Imaging of Adenosine 2A Receptors in Neuroinflammatory and Neurodegenerative Disease

Contrast Media & Molecular Imaging ◽

10.1155/2017/6975841 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 13

Author(s):

Anna Vuorimaa ◽

Eero Rissanen ◽

Laura Airas

Keyword(s):

Immune System ◽

Pet Imaging ◽

Neurological Diseases ◽

Suppressive Effect ◽

Receptor Targeting ◽

Additional Tool ◽

Positron Emission ◽

The Central Nervous System ◽

G Protein Coupled

Adenosine receptors are G-protein coupled P1 purinergic receptors that are broadly expressed in the peripheral immune system, vasculature, and the central nervous system (CNS). Within the immune system, adenosine 2A (A2A) receptor-mediated signaling exerts a suppressive effect on ongoing inflammation. In healthy CNS,A2Areceptors are expressed mainly within the neurons of the basal ganglia. Alterations inA2Areceptor function and expression have been noted in movement disorders, and in Parkinson’s disease pharmacologicalA2Areceptor antagonism leads to diminished motor symptoms. AlthoughA2Areceptors are expressed only at a low level in the healthy CNS outside striatum, pathological challenge or inflammation has been shown to lead to upregulation ofA2Areceptors in extrastriatal CNS tissue, and this has been successfully quantitated usingin vivopositron emission tomography (PET) imaging andA2Areceptor-binding radioligands. Several radioligands for PET imaging ofA2Areceptors have been developed in recent years, andA2Areceptor-targeting PET imaging may thus provide a potential additional tool to evaluate various aspects of neuroinflammationin vivo. This review article provides a brief overview ofA2Areceptors in healthy brain and in a selection of most important neurological diseases and describes the recent advances inA2Areceptor-targeting PET imaging studies.

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PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives

Molecules ◽

10.3390/molecules25174017 ◽

2020 ◽

Vol 25 (17) ◽

pp. 4017

Author(s):

Santosh Reddy Alluri ◽

Sung Won Kim ◽

Nora D. Volkow ◽

Kun-Eek Kil

Keyword(s):

Nervous System ◽

Adrenergic Receptors ◽

Systems Research ◽

History Of Research ◽

Positron Emission ◽

History Of ◽

The Central Nervous System ◽

Pet Radiotracers ◽

The Brain

Epinephrine (E) and norepinephrine (NE) play diverse roles in our body’s physiology. In addition to their role in the peripheral nervous system (PNS), E/NE systems including their receptors are critical to the central nervous system (CNS) and to mental health. Various antipsychotics, antidepressants, and psychostimulants exert their influence partially through different subtypes of adrenergic receptors (ARs). Despite the potential of pharmacological applications and long history of research related to E/NE systems, research efforts to identify the roles of ARs in the human brain taking advantage of imaging have been limited by the lack of subtype specific ligands for ARs and brain penetrability issues. This review provides an overview of the development of positron emission tomography (PET) radiotracers for in vivo imaging of AR system in the brain.

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Faculty Opinions recommendation of Real-time in vivo imaging of fungal migration to the central nervous system.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717957672.793462077 ◽

2012 ◽

Author(s):

Stéphane Bretagne ◽

Alexandre Alanio

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Real Time ◽

In Vivo Imaging ◽

The Central Nervous System

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Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

EJNMMI Physics ◽

10.1186/s40658-019-0263-x ◽

2019 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Carlos Velasco ◽

Adriana Mota-Cobián ◽

Jesús Mateo ◽

Samuel España

Keyword(s):

Positron Emission Tomography ◽

Blood Sample ◽

Pet Imaging ◽

Spectroscopic Analysis ◽

Gamma Spectroscopy ◽

Emission Tomography ◽

Blood Samples ◽

Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

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Correction to: In vivo imaging of early stages of rheumatoid arthritis by α5β1-integrin-targeted positron emission tomography

EJNMMI Research ◽

10.1186/s13550-019-0582-x ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Johannes Notni ◽

Florian T. Gassert ◽

Katja Steiger ◽

Peter Sommer ◽

Wilko Weichert ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Positron Emission Tomography ◽

In Vivo Imaging ◽

Emission Tomography ◽

Early Stages ◽

Positron Emission ◽

Α5β1 Integrin

Following publication of the original article [1], the authors have reported an error in the ‘Histopathology’ (under ‘Materials and methods’) section of the article that compromises the reproducibility of the paper.

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Positron emission tomography reporter gene strategy for use in the central nervous system

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901645116 ◽

2019 ◽

Vol 116 (23) ◽

pp. 11402-11407 ◽

Cited By ~ 9

Author(s):

Tom Haywood ◽

Corinne Beinat ◽

Gayatri Gowrishankar ◽

Chirag B. Patel ◽

Israt S. Alam ◽

...

Keyword(s):

Positron Emission Tomography ◽

Central Nervous System ◽

Nervous System ◽

Reporter Gene ◽

Pet Imaging ◽

Emission Tomography ◽

Great Promise ◽

Adeno Associated Virus ◽

Positron Emission ◽

The Central Nervous System

There is a growing need for monitoring or imaging gene therapy in the central nervous system (CNS). This can be achieved with a positron emission tomography (PET) reporter gene strategy. Here we report the development of a PET reporter gene system using the PKM2 gene with its associated radiotracer [18F]DASA-23. The PKM2 reporter gene was delivered to the brains of mice by adeno-associated virus (AAV9) via stereotactic injection. Serial PET imaging was carried out over 8 wk to assess PKM2 expression. After 8 wk, the brains were excised for further mRNA and protein analysis. PET imaging at 8 wk post-AAV delivery showed an increase in [18F]DASA-23 brain uptake in the transduced site of mice injected with the AAV mice over all controls. We believe PKM2 shows great promise as a PET reporter gene and to date is the only example that can be used in all areas of the CNS without breaking the blood–brain barrier, to monitor gene and cell therapy.

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