Imaging the neurochemical brain in health and disease

Neurochemical transmission is a fundamental element of brain organisation that has been relatively unexplored in the living human brain. Continuing advances in radionuclide imaging, particularly positron emission tomography (PET) and single photon emission tomography (SPET), mean that elements of neurochemical transmission can now be directly measured in vivo. With these techniques convincing abnormalities of monoaminergic neurotransmitter systems have been revealed in illnesses such as Parkinson's disease and schizophrenia. Furthermore, mechanisms of drug action and treatment responses can be monitored in vivo. This brief review describes some of our recent attempts to image the neurochemical brain in health and disease at the MRC Cyclotron Unit, Hammersmith Hospital, London.     

Confirmation of Specific Binding of the 18-kDa Translocator Protein (TSPO) Radioligand [18F]GE-180: a Blocking Study Using XBD173 in Multiple Sclerosis Normal Appearing White and Grey Matter

Molecular Imaging and Biology - Measurements of non-displaceable binding (VND) of positron emission tomography (PET) ligands are not often made in vivo in humans because they require ligands to...     

Quantitative and Visual Assessments toward Potential Sub-mSv or Ultrafast FDG PET Using High-Sensitivity TOF PET in PET/MRI

Molecular Imaging and Biology - Newer high-performance time-of-flight (TOF) positron emission tomography (PET) systems have the capability to preserve diagnostic image quality with low count...     

Imaging Non-Dopaminergic Function in Parkinson’s Disease

In Parkinson’s disease (PD), there is degeneration of the cholinergic, noradrenergic, and serotonergic systems in addition to dopaminergic projections. Function of these non-dopaminergic systems can be imaged with positron emission tomography (PET) and single photon emission computed tomography (SPECT) and correlated with motor and nonmotor symptomatology. In addition, neuronal loss in PD is associated with microglial activation. The role of microglia in driving the disease process remains uncertain. This review presents and discusses current findings in these areas.     

Contraction-induced [18F]-fluoro-deoxy-glucose uptake can be measured in human calf muscle using high-resolution PET

Contraction-induced glucose uptake can be imaged and quantified by the use of positron emission tomography (PET). In the human extremities, such data may reveal important information regarding the in vivo mechanical function of e.g. the force transmitting tissues such as tendons. However, to investigate structures of limited size, a PET scanner with high resolution is required. We tested the potential of the recently developed high-resolution brain PET scanner (ECAT HRRT) for imaging of human lower extremities. [18F]-fluoro-deoxy-glucose uptake following voluntary and stimulated isometric muscle contractions was studied in a 30-year-old male. The results showed that the activated muscle or muscles are clearly delineated in the high-resolution PET images. Furthermore, the load-induced gain in tendon uptake was clearly visualized. In conclusion, the HRRT scanner is an appropriate tool for investigating physiological processes within the human extremities, and the very high resolution yields a potential for more accurate conclusions when target tissues are limited in size.     

Functional genomics and radioisotope-based imaging procedures

After the sequencing of the human genome has been completed, non-invasive imaging studies are needed to assess the function of new genes in living organisms. The evaluation of genetically manipulated animals or new designed biomolecules will require a thorough understanding of physiology, biochemistry and pharmacology, and the experimental approaches will involve many new technologies including in vivo imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET). Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as enzymes, receptors, antigens or transporters. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging. Also, drug distribution studies for new therapeutic biomolecules are needed at least during preclinical stages of drug development. Clinical gene therapy needs non-invasive tools to evaluate the efficiency of gene transfer. These informations can be used for therapy planning, follow-up studies in treated tumors and as an indicator of prognosis. Therapy planning is performed by the assessment of gene expression for example using radio-labeled specific substrates to determine the activity of suicide enzymes such as the Herpes Simplex Virus thymidine kinase. Follow-up studies with single photon emission tomography or positron emission tomography may be done to evaluate early or late effects of gene therapy on tumor metabolism or proliferation. Finally, new biomolecules will be developed by bioengineering methods which may be used for isotope-based diagnosis and treatment of disease.     

PET与伽玛PET在癫痫灶定位中的应用

就正电子发射断层成像 (PET)与伽玛PET在癫痫灶定位中的应用作一介绍     

Performance Evaluation of a Newly Developed MR-Compatible Mobile PET Scanner with Two Detector Layouts

Molecular Imaging and Biology - A mobile positron emission tomography (PET) scanner called flexible PET (fxPET), designed to fit existing magnetic resonance imaging (MRI) or computed tomography...     

Advances in neuroimaging research on Asperger syndrome

Autism spectrum disorder (ASD) (i.e., autism and Asperger syndrome) is a neurodevelopmental disorder, although its etiology is still unclear. Neuroimaging studies have attempted to identify the neurobiological basis of ASD. This article reviews recent progress in ASD research using magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). MRI studies documented structural and functional abnormalities in cerebella, the frontal lobes, the temporal lobes, and limbic systems of individuals with ASD. SPECT and PET studies suggested that abnormalities of the serotonergic system, in addition to decreased regional cerebral blood flow in the frontal and temporal lobes, are implicated in the pathophysiology of ASD.     

Prognostic value of preoperative fluorodeoxyglucose positron emission tomography/computed tomography in patients with potentially resectable pancreatic cancer

Abdominal Radiology - To evaluate the prognostic value of preoperative 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with potentially...     

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Following Chimeric Antigen Receptor T-cell Therapy in Large B-cell Lymphoma

Molecular Imaging and Biology - 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a well-established imaging modality to assess responses in patients with...     

Prognostic Impact of Intratumoral Heterogeneity Based on Fractal Geometry Analysis in Operated NSCLC Patients

Molecular Imaging and Biology - To determine the heterogeneity of glucose uptake applying fractal analysis on positron emission tomography/computed tomography (PET/CT) with...     

Functional genomics and radioisotope-based imaging procedures

After the sequencing of the human genome has been completed, non-invasive imaging studies are needed to assess the function of new genes in living organisms. The evaluation of genetically manipulated animals or new designed biomolecules will require a thorough understanding of physiology, biochemistry and pharmacology, and the experimental approaches will involve many new technologies including in vivo imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET). Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as enzymes, receptors, antigens or transporters. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging. Also, drug distribution studies for new therapeutic biomolecules are needed at least during preclinical stages of drug development. Clinical gene therapy needs non-invasive tools to evaluate the efficiency of gene transfer. These informations can be used for therapy planning, follow-up studies in treated tumors and as an indicator of prognosis. Therapy planning is performed by the assessment of gene expression for example using radio-labeled specific substrates to determine the activity of suicide enzymes such as the Herpes Simplex Virus thymidine kinase. Follow-up studies with single photon emission tomography or positron emission tomography may be done to evaluate early or late effects of gene therapy on tumor metabolism or proliferation. Finally, new biomolecules will be developed by bioengineering methods which may be used for isotope-based diagnosis and treatment of disease.     

Hunting for the high-affinity state of G-protein-coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging

The concept of the high-affinity state postulates that a certain subset of G-protein-coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmission to pharmacological or physiological stimuli and the dysregulation of neurotransmission in neurological or psychiatric disorders. The high-affinity state is preferentially recognized by agonists in vitro. For this reason, agonist tracers have been developed as tools for the noninvasive imaging of the high-affinity state with positron emission tomography (PET). This review provides an overview of agonist tracers that have been developed for PET imaging of the brain, and the experimental paradigms that have been developed for the estimation of the relative abundance of receptors configured in the high-affinity state. Agonist tracers appear to be more sensitive to endogenous neurotransmitter challenge than antagonists, as was originally expected. However, other expectations regarding agonist tracers have not been fulfilled. Potential reasons for difficulties in detecting the high-affinity state in vivo are discussed.     

Positron emission tomography and drug discovery: contributions to the understanding of pharmacokinetics, mechanism of action and disease state characterization.

As an imaging modality, positron emission tomography (PET) provides unique quantitative in vivo information of value to drug discovery studies. These non-invasive studies span the pharmacokinetic/pharmacodynamic evaluation of potential drug candidates, receptor occupancy as an important determinant of efficacy, the pharmacological characterization of potential mechanisms of action, and the biological characterization of disease with well-characterized PET ligands. PET techniques are also being applied to the assessment of gene-level activities and the longitudinal evaluation of disease progression and therapeutic intervention. As the availability of PET scanners, cyclotrons, and specific PET ligands grows, the techniques highlighted in this review will become central to target validation, drug candidate selection, pharmacokinetic characterization, and clinical evaluation.     

Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier

The blood-brain barrier (BBB) permeabilities of 11 compounds were measured both in vitro with a newly developed coculture-based model of human BBB and in vivo with positron emission tomography (PET). The 11 compounds were fluoropyridinyl derivatives labeled with the positron-emitter fluorine-18, [(18)F]F-A-85380 [2-[(18)F]fluoro-3-[2(S)-2 azetidinylmethoxy]pyridine], and 10 selected N-substituted-azetidinyl and pyrrolidinyl closely related [(18)F]fluoropyridinyl derivatives (including [N'-aromatic/aliphatic]-thioureas, -ureas, and -amides). The in vitro BBB model, a new coculture system of primary human brain endothelial cells and astrocytes, was used to measure the permeability coefficient for each compound. Dynamic PET studies were performed in rats with the same compounds, and a two-compartment model analysis was used to calculate their in vivo permeability coefficients. The 11 derivatives differed in their degree of BBB passage and transport mechanism. The analysis of PET data showed a significant cerebral uptake for six derivatives, for which the in vitro evaluation indicated active influx or free diffusion. Five derivatives displayed low in vivo cerebral uptake, in agreement with the observation of an in vitro active efflux. Overall, there was a remarkable correlation between the in vitro and in vivo permeability coefficients (r = 0.99). This double study proves a close correlationship between the assessment of the BBB passage in vitro and in vivo. The in vitro model of human BBB offers the possibility of subtle discrimination of various BBB permeability degrees and transport mechanisms. Conversely, small animal PET imaging appears suitable to screen directly in vivo brain targeting of drugs or radiopharmaceutical candidates.     

Zero-Extra-Dose PET Delayed Imaging with Data-Driven Attenuation Correction Estimation

Molecular Imaging and Biology - Delayed positron emission tomography (PET) imaging may improve sensitivity and specificity in lesion detection. We proposed a PET data-driven method to estimate the...     

PET scanners dedicated to molecular imaging of small animal models.

The dramatic advances of biological research in recent years that have focused on the molecular basis of how systems of the body (e.g. cells, organs and the whole organism) function, have increased the need for molecular imaging instrumentation. Of the several imaging modalities available today applied for in vivo studies of research animals, positron emission tomography (PET) is a technique that permits non-invasive use of positron labeled molecular imaging probes to image and assay biochemical processes of cellular function in the living subject. Imaging can be performed repeatedly before and after interventions and therefore allows the use of each animal as its own control. Many different positron labeled compounds have been and continue to be synthesized as probes that target a range of molecular targets within specific biochemical pathways. These molecular imaging probes are used in extremely low mass amounts, such that biological processes involving compounds in nanomolar concentration or lower can be imaged without disturbing the process. Biological processes from receptors and synthesis of transmitters in cell communication pathways, to metabolic processes and gene expression can be imaged. In the past, PET in animal research has been used extensively for studies of primates and larger animals. In recent years, the development of new detector technology has lowered the limits of spatial resolution. This has made it possible to use PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents some of the challenges facing small animal PET technology, provides an overview of the development of small animal PET systems, and discusses the current state of the art technology, some of its applications, as well as some future directions.     

Proceedings of the World Molecular Imaging Congress 2019, Montreal Quebec,Canada September 4-7, 2019: General Abstracts

Molecular Imaging and Biology - The applications of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/X-ray computed tomography (PET/CT) in the management of patients with breast cancer...