Positron emission tomographic study of the brain during involuntary syntactic processing

A positron emission tomography (PET) method was used to study the human brain for involuntary processing of syntactically organized information. Eight healthy subjects counted a certain letter in a running line presented on a monitor screen. PET scanning was conducted during this task performance. In cases when the running line presented a syntactically coherent text (unlike the cases when the same task was performed during administration of a sequence of incoherent words, pseudowords, or pseudotext), PET scanning revealed activation in the temporal and temporoparietooccipital cortical areas of the left hemisphere and the right temporal pole. The inverse comparison demonstrated activation in the left occipital area probably connected with the purely visual strategy of the task performance. These results show that information presentation in the form of coherent text even without the instruction to read the text is associated with more profound involuntary linguistic stimuli processing than the presentation of incoherent words, pseudowords, or pseudotext. The activation of the polar anterior temporal areas is considered evidence for activation of the system of syntactic processing, which functioned, in this case, in the involuntary (automatic) mode.     

Positron emission tomography in patients with clinically diagnosed Alzheimer's disease.

Fourteen patients who had clinically diagnosed Alzheimer''s disease with mild to severe dementia (mean age 69.1 years) were evaluated by calculation of local cerebral metabolic rate for glucose (LCMR-gl) based on uptake of 18F-2-fluoro-2-deoxyglucose (FDG) detected with positron emission tomography (PET). PET scanning showed that the patients had significantly lower LCMR-gl values than 11 age-matched neurologically normal volunteers (mean age 66.3 years). The differences were most marked in the temporal cortex, followed by the frontal, parietal and occipital cortex. In each case the LCMR-gl value was below the lowest control value in at least one cortical area and usually in several; the reduction in LCMR-gl and the number of regions involved in the patients increased with the severity of the dementia. Deficits noted in neuropsychologic testing generally correlated with those predicted from loss of regional cortical metabolism. The patients with Alzheimer''s disease were also examined with magnetic resonance imaging, computed tomography or both; the degree of atrophy found showed only a poor correlation with the neuropsychologic deficit. Significant atrophy was also noted in some of the controls. A detailed analysis of LCMR-gl values in selected cerebral regions of various sizes refuted the hypothesis that the reduction in cortical glucose metabolism in Alzheimer''s disease is due to the filling by metabolically inert cerebrospinal fluid of space created by tissue atrophy.     

Positron emission tomography imaging of prostate cancer

Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. Positron emission tomography (PET), a non-invasive, sensitive, and quantitative imaging technique, can facilitate personalized management of PCa patients. There are two critical needs for PET imaging of PCa, early detection of primary lesions and accurate imaging of PCa bone metastasis, the predominant cause of death in PCa. Because the most widely used PET tracer in the clinic, ¹⁸F-fluoro-2-deoxy-2-d-glucose (¹⁸F-FDG), does not meet these needs, a wide variety of PET tracers have been developed for PCa imaging that span an enormous size range from small molecules to intact antibodies. In this review, we will first summarize small-molecule-based PET tracers for PCa imaging, which measure certain biological events, such as cell membrane metabolism, fatty acid synthesis, and receptor expression. Next, we will discuss radiolabeled amino acid derivatives (e.g. methionine, leucine, tryptophan, and cysteine analogs), which are primarily based on the increased amino acid transport of PCa cells. Peptide-based tracers for PET imaging of PCa, mostly based on the bombesin peptide and its derivatives which bind to the gastrin-releasing peptide receptor, will then be presented in detail. We will also cover radiolabeled antibodies and antibody fragments (e.g. diabodies and minibodies) for PET imaging of PCa, targeting integrin α_vβ₃, EphA2, the epidermal growth factor receptor, or the prostate stem cell antigen. Lastly, we will identify future directions for the development of novel PET tracers for PCa imaging, which may eventually lead to personalized management of PCa patients.     

Positron emission tomographic evaluation of the putative dopamine-D3 receptor ligand, [11C]RGH-1756 in the monkey brain

The dopamine-D3 receptor is of special interest due to its postulated role in the pathophysiology and treatment of schizophrenia and Parkinson's Disease. Increasing evidences support the assumption that the D3 receptors are occupied to a high degree by dopamine at physiological conditions. Research on the functional role of the D3 receptors in brain has however been hampered by the lack of D3 selective ligands. In the present Positron Emission Tomography (PET) study the binding of the novel, putative dopamine-D3 receptor ligand, [11C]RGH-1756 was characterized in the cynomolgus monkey brain. [11C]RGH-1756 was rather homogenously distributed in brain and the regional binding potential (BP) values ranged between 0.17 and 0.48. Pretreatment with unlabelled RGH-1756 decreased radioligand binding to the level of the cerebellum in most brain areas. The regional BP values were lower after intravenous injection of a higher mass of RGH-1756, indicating saturable binding of [11C]RGH-1756. The D2/D3 antagonist raclopride partly inhibited the binding of [11C]RGH-1756 in several brain areas, including the striatum, mesencephalon and neocortex, whereas the 5HT(1A) antagonist WAY-100635 had no evident effect on [11C]RGH-1756 binding. Despite the promising binding characteristics of RGH-1756 in vitro the present PET-study indicates that [11C]RGH-1756 provides a low signal for specific binding to the D3 receptor in vivo. One explanation is that the favorable binding characteristics of RGH-1756 in vitro are not manifested in vivo. Alternatively, the results may support the hypothesis that the dopamine-D3 receptors are indeed occupied to a high extent by dopamine in vivo and thus not available for radioligand binding.     

Positron emission tomography: a clinical and biological research tool

Medical and biological imaging has undergone a revolution in the past decade. Positron emission tomography (PET) has been developed to visualize biochemical and physiological phenomena in living humans and animals. For instance, blood flow, blood volume, glucose metabolism, amino acid metabolism, can be quantitatively estimated by means of PET with various radioactive tracers. This functional and molecular imaging technique has progressed rapidly from being a research technique in laboratories to a routine clinical imaging modality. The most widely used radiotracer in routine is 18F-fluorodeoxyglucose (18FDG), which is an analogue of glucose. Since glucose metabolism is increased many fold in malignant tumors, PET has a major role in the field of clinical oncology and recently in cardiology and neurology. PET is also a valuable tool to study cerebral or cardiac binding sites and to image the expression of reporter genes in small animals. In this review, we summarize the most recent developments in PET imaging with particular reference to the radiotracers available and their application.     

Positron emission tomography: imaging and quantification of neurotransporter availability

Over the last decade, a large number of radiotracers have been developed to image and quantify transporter availability with positron emission tomography (PET) or single-photon emission computed tomography (SPECT). Radiotracers suitable to image dopamine transporters (DATs) and serotonin transporters (SERTs) have been the object of most efforts. Following a brief overview of DAT and SERT radiotracers that have been demonstrated to be suitable for quantitative analysis in vivo, this article describes the principal methods that have been used for the analysis of these data. Kinetic modeling is the most direct implementation of the compartment models, but with some tracers accurate input function measurement and good compartment configuration identification can be difficult to obtain. Other methods were designed to overcome some particular vulnerability to error of classic kinetic modeling, but introduced new vulnerabilities in the process. Reference region methods obviate the need for arterial plasma measurement, but are not as robust to violations of the underlying modeling assumptions as methods using the arterial input function. Graphical methods give estimates of distribution volumes without the requirement of compartment model specification, but provide a biased estimator in the presence of statistical noise. True equilibrium methods are quite robust, but their use is limited to experiments with tracers that are suitable for constant infusion. In conclusion, no universally "best" method is applicable to all neurotransporter imaging studies, and careful evaluation of model-based methods is required for each radiotracer.     

Positron emission tomography in venous ulceration and liposclerosis: study of regional tissue function.

Oxygen-15 administered by continuous inhalation and emission computed tomography were used to study regional tissue oxygen utilisation and blood flow in the limbs of 11 patients with venous ulceration and five patients with liposclerosis due to venous insufficiency. The results showed increased blood flow and appreciably reduced fractional oxygen extraction in the diseased tissues. These findings indicated a local, functional shunting of blood through the abnormal microcirculation of the skin and subcutaneous tissues. This may be an important factor in the aetiology of the skin changes seen in patients with calf muscle pump failure.     

Review. Positron emission tomography imaging studies of dopamine receptors in primate models of addiction

Animal models have provided valuable information related to trait and state variables associated with vulnerability to drug addiction. Our brain imaging studies in monkeys have implicated D2 receptors in cocaine addiction. For example, an inverse relationship between D2 receptor availability and rates of cocaine self-administration has been documented. Moreover, environmental variables, such as those associated with formation of the social hierarchy, can impact receptor availability and sensitivity to the abuse-related effects of cocaine. Similarly, both D2 receptor availability and cocaine self-administration can be altered by chronic drug administration and fluctuations in hormone levels. In addition, cocaine self-administration can be altered in an orderly fashion by presentation of an acute stressor, such as acting as an intruder into an unfamiliar social group, which can shift the cocaine dose-response curve to the left in subordinate monkeys and to the right in dominant animals, suggesting an interaction between social variables and acute stressors. Conversely, irrespective of social rank, acute environmental enrichment, such as increasing the size of the living space, shifts the cocaine dose-response curve to the right. These findings highlight a pervasive influence of the environment in modifying the reinforcing effects of cocaine and strongly implicate brain D2 receptors.     

Positron emission tomography: the conceptual idea using a multidisciplinary approach

Positron emission tomography (PET) is a method for quantitatively measuring biochemical and physiological processes in vivo by using radiopharmaceuticals labeled with positron-emitting radionuclides such as 11C, 13N, 15O, and 18F and by measuring the annihilation radiation using a coincidence technique. This technique is also used for measurement of the pharmacokinetics of labeled drugs and measurement of the effects of drugs on metabolism. Deviations from normal metabolism can be measured and insight into biological processes responsible for diseases can be obtained.     

Positron emission tomography neuroreceptor imaging as a tool in drug discovery, research and development.

Improved communication and cooperation between research-driven drug companies and academic positron emission tomography (PET) centers, coupled with improvements in PET camera resolution, the availability of small animal PET cameras and a growing list of neuroreceptor-specific PET tracers, have all contributed to a substantial increase in the use and value of PET as a tool in central nervous system drug discovery and development.