18F-fluorodeoxyglucose positron emission tomography and the prognosis of patients with pancreatic adenocarcinoma

BACKGROUND: Fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) can be used to measure the glycolytic activity of tumor cells. Though the prognosis of patients with pancreatic adenocarcinoma is usually poor, a subset of patients with good prognoses may be discovered by determining the degree of FDG integration into tumors. METHODS: Fourteen patients with histologically proven pancreatic adenocarcinoma underwent 18F-FDG PET. The standardized uptake value (SUV) of 18F-FDG was calculated, and the patients were divided into high (> or = 3.0) and low (< 3.0) SUV groups. RESULTS: The two groups were not significantly different in terms of age, tumor location and size, staging, and treatment. However, analysis by the Kaplan-Meier method revealed that the groups had different prognoses (log rank test, P < 0.05). The mean survival of patients with high SUV was 5 months, whereas that of patients with low SUV was 14 months. There were not strong correlations between the SUVs and tumor size (0.56), serum carbohydrate antigen 19-9 (0.39), or carcinoembryonic antigen (0.52). CONCLUSIONS: SUV calculated with 18F-FDG can be utilized as a prognostic factor for patients with pancreatic adenocarcinoma.     

Attenuation-corrected 99mTc-tetrofosmin single-photon emission computed tomography in the detection of viable myocardium: comparison with positron emission tomography using 18F-fluorodeoxyglucose

OBJECTIVES: The purpose of this study was to assess the efficacy of attenuation-corrected (AC) technetium-99m (99mTc)-tetrofosmin single-photon emission computed tomography (SPECT) in detecting viable myocardium compared to 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND: The role of 99mTc-labeled perfusion tracers in the assessment of myocardial viability remains controversial. Attenuation artifacts affect the diagnostic accuracy of SPECT images. METHODS: Twenty-four patients with coronary artery disease (mean left ventricular ejection fraction 30%) underwent resting 99mTc-tetrofosmin SPECT and FDG PET imaging. Both AC and non-attenuation-corrected (NC) SPECT images were generated. RESULTS: Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG on the patient basis increased from 79.8%+/-14.0% (mean+/-SD) on the NC images to 90.8%+/-10.6% on the AC images (p=0.002). The percentage of 99mTc-tetrofosmin defect segments within PET-viable segments, an estimate for the degree of underestimation of viability, decreased from 19.8%+/-15.2% on the NC images to 9.7%+/-12.6% on the AC images (p=0.01). Similar results were obtained when a 60% threshold was used to define viability by FDG PET. When the anterior-lateral and inferior-septal regions were separately analyzed, the effect of attenuation correction was significant only in the inferior-septal region. CONCLUSIONS: The results indicate that AC 99mTc-tetrofosmin SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability particularly in the inferior-septal region, although some underestimation/overestimation of viability may still occur even with attenuation correction.     

Clinical positron emission tomography for brain tumors: comparison of fludeoxyglucose F 18 and L-methyl-11C-methionine

PURPOSE: To evaluate the differences between fludeoxyglucose F 18 (FDG) and L-methyl-11C-methionine (11C-methionine) as tracers for positron emission tomography (PET) in the evaluation of brain tumors. METHODS: We analyzed 10 patients with histologically verified cerebral glioma or meningioma and 1 patient with a neuroradiologic diagnosis of low-grade glioma by using FDG, 11C-methionine, and PET. We qualitatively and quantitatively evaluated the extent and degree of accumulation of FDG and 11C-methionine in the tumor tissue. RESULTS: Although PET with FDG depicted malignant tumors as a hot spot in all cases, it was not able to delineate the extent of the tumor. Conversely, PET with 11C-methionine outlined the tumors as areas of increased accumulation of 11C-methionine, regardless of the degree of malignancy. CONCLUSION: PET with FDG and with 11C-methionine can play complementary roles in the evaluation of brain tumors.     

Ketamine increases the striatal N-[11C]methylspiperone binding in vivo: positron emission tomography study using conscious rhesus monkey

A system for positron emission tomography study of conscious monkeys was newly developed. By use of this system in combination with a microdialysis technique, the effect of ketamine on the binding and release of dopamine was investigated. The administration of ketamine (5 mg/kg) caused sedation accompanied by psychotic symptoms such as nystagmus and stereotyped movements of extremities. During this psychotomimetic period produced by ketamine, a significant increase in the accumulation of the dopamine D2 receptor ligand N-[11C]methylspiperone was observed in the striatum compared with the level in the conscious state, while no significant change was observed in the frontal cortex and cerebellum. In contrast to the use of ketamine as the anesthetic, pentobarbital (25 mg/kg), which produced deeper anesthesia but no psychotic symptoms, caused a decrease in the accumulation of N-[11C]methylspiperone in the striatum. Kinetic analysis, conducted by a graphical method, revealed that the value of the association constant (K3) for N-[11C]methylspiperone binding in the striatum was increased to approximately 130% by ketamine and decreased to approximately 70% by pentobarbital compared with the control values. Furthermore, the release of dopamine from the striatum measured by microdialysis was not affected by ketamine anesthesia. These results indicate that ketamine facilitates striatal dopaminergic neurotransmission through increasing the binding activity of dopamine D2 receptors in the striatum, and suggest that these changes may be related to the psychotomimetic behavioral symptoms of this drug.     

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca's area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern.     

Effects of m-chlorophenylpiperazine on regional brain glucose utilization: a positron emission tomographic comparison of alcoholic and control subjects

m-Chlorophenylpiperazine (mCPP) is a mixed serotonin agonist/antagonist used extensively in psychiatric research. Alcoholics show blunted neuroendocrine responses to mCPP, and in some settings mCPP can induce craving for alcohol, particularly among early onset alcoholics. We used 2-[18F]-2-deoxy-D-glucose positron emission tomography to examine the effects of intravenously administered mCPP (0.08 mg/kg) on brain glucose utilization in a group of 18 male alcoholics and 12 healthy male control subjects. Differences between two sequential scans (the first followed placebo and the second followed mCPP) were evaluated statistically with a Gaussian random field-based method. Among healthy volunteers mCPP significantly increased brain glucose metabolism in the right medial and posterior orbital gyrus, the cerebellar hemispheres bilaterally, the left nucleus accumbens, the head of the caudate nucleus bilaterally, the anterior and medial-dorsal nuclei of the thalamus bilaterally, the middle frontal gyrus, the left insular cortex, the left middle temporal gyrus, and the posterior cingulate gyrus. Among alcoholic subjects mCPP significantly increased brain glucose metabolism in larger areas of the cerebellum and posterior cingulate than it did in healthy volunteers, but compared with the healthy volunteers, alcoholics showed a smaller area of mCPP-induced activation in the thalamus, almost no activation in the orbital cortices, and no activation at all in the head of the caudate nucleus or the middle frontal gyrus. These results suggest that a serotoninergic challenge activates basal ganglia circuits involving orbital and prefrontal cortices among healthy volunteers but that the response of these circuits is blunted among alcoholics.     

DOPA decarboxylase activity in attention deficit hyperactivity disorder adults. A [fluorine-18]fluorodopa positron emission tomographic study

Converging evidence implicates the dopaminergic system and the prefrontal and nigrostriatal regions in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Using positron emission tomography (PET) with [fluorine-18]fluorodopa (F18-DOPA), we compared the integrity of the presynaptic dopaminergic function between 17 ADHD adults and 23 healthy controls. The ratio of the isotope concentration of specific regions to that of nonspecific regions reflects DOPA decarboxylase activity and dopamine storage processes. Of three composite regions (prefrontal cortex, striatum, and midbrain), only the prefrontal cortex showed significantly different F18-DOPA ratios in ADHD as compared with control adults (p < 0.01). The medial and left prefrontal areas were the most altered (lower F18-DOPA ratios by 52 and 51% in ADHD as compared with controls). Similarly, the interaction [sex x diagnosis] was significant only in the prefrontal cortex (p < 0.02): lower ratios in men than in women in ADHD and vice versa in controls. These findings suggest that a prefrontal dopaminergic dysfunction mediates ADHD symptoms in adults and that gender influences this abnormality. On the basis of previous neuroimaging findings in ADHD showing discrepant findings in adults and adolescents and on evidence for midbrain dopaminergic defect in adolescents, we hypothesize that the prefrontal dopaminergic abnormality in ADHD adults is secondary and results from an interaction of the primary subcortical dopaminergic deficit with processes of neural maturation and neural adaptation.     

Imaging proliferation in vivo with [F-18]FLT and positron emission tomography

Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.     

Limbic dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography

BACKGROUND: Diagnostic classes (derived from CATEGO) can be correlated with regional brain metabolism in patients with major psychiatric disorders. METHOD: Seventeen patients with schizophrenia, 15 with mania, 10 with depression and 10 healthy Volunteers were examined with positron emission tomography (PET) and 18F-labelled fluorodeoxyglucose, as a marker for glucose metabolism. The number of possible comparisons of regions of interest was reduced by principal-components analysis, and differences in factor scores were determined between diagnostic groups. RESULTS: Four independent factors, representing distributed brain systems, emerged: an anterior-posterior (1), a left-right temporal (2), a temporofrontal (3), and a mediofrontal (4) system, of which (1), (2) and (3) were abnormal in schizophrenia, (1) and (2) in mania, and (1) in depression. CONCLUSIONS: Abnormal patterns of metabolism could be detected, in decreasing order, in schizophrenia, mania and depression. Some of these abnormalities are likely to be due to medication, but others will be associated with structural or functional abnormalities of the frontolimbic system in the diagnostic groups.     

11C]beta-CIT-FE, a radioligand for quantitation of the dopamine transporter in the living brain using positron emission tomography

Patients with gastrointestinal hemorrhage are frequently admitted to critical care units, in large part to be observed for signs of hemodynamic instability. All patients admitted with gastrointestinal bleeding to our medical intensive care unit over a 1-year period (n=108) were retrospectively reviewed to determine the incidence of hemodynamic instability. In an elderly patient population with predominantly nonvariceal bleeding, only 13% of those admitted had documented hypotension that led to an intervention. Only 7% had clinically significant hypotension after the first 5 hours of admission. Admission clinical criteria were analyzed by multivariate analysis but could not reliably predict patients at increased risk for hemodynamic instability. However, patients without significant comorbid illness who have been endoscopically shown to have a low-risk lesion can be considered for early transfer to a regular bed after a short period of close observation. This could lead to better resource utilization and cost savings without jeopardizing patient care.     

Cerebral perfusion and oxygen metabolism in Parkinson's disease: positron emission tomographic study using oxygen-15-labeled CO2 and O2]

In many previous studies, positron emission tomography (PET) has been used to evaluate cerebral perfusion and oxygen metabolism in Parkinson's disease. In this article, these previous reports are reviewed together with our recent findings. Hypoperfusion and hypometabolism in parkinsonian brains reported previously seemed to be derived chiefly from psychiatric manifestations, including intellectual decline and depression. In our study on 34 patients with asymmetric symptoms, the blood flow and oxygen metabolism were significantly higher in the caudate head and putamen, contralateral to the predominant patient's symptoms, than in the opposite nuclei. The asymmetry in the perfusion and metabolism is clearer in the early stage of the disease or in patients without DOPA therapy. These findings suggest that the striatal dysfunction is caused by uninhibited activities, supersensitivities, or compensatory hyperactivities of the striatum.     

Fear conditioning and brain activity: A positron emission tomography study in humans.

Regional cerebral blood flow (rCBF) was measured with H? 1?O positron emission tomography in 8 healthy women before and after fear conditioning (i.e., paired shocks) and unpaired shocks to videotape cues. Conditioning was supported by enhanced peripheral nervous system recordings and subjective ratings. Fear conditioning increased rCBF in the central gray of the midbrain; bilaterally in the hypothalamus, the thalamus, and the left striatum; and in the right and left anterior cingulate and right prefrontal cortices. Regional CBF was attenuated bilaterally in the right and left prefrontal, temporal (including the amygdala), parietal, and occipital cortices, and in the left orbitofrontal cortex. When compared with unpaired shock presentations, fear conditioning resulted in elevated rCBF in the left cerebellum. Hence, in the present paradigm, only neural activity in the left cerebellum solely reflected processes associated with true Pavlovian conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Quantitation of carbon-11-labeled raclopride in rat striatum using positron emission tomography

Using conventional autoradiographic and tissue counting techniques, the experimental quantitation of in vivo kinetics of prospective or established radioligands for PET is animal and labour intensive. The present study tested the feasibility of using PET itself to quantitate the specific binding of [11C]raclopride to rat striatum and to study the effects of experimental manipulation of endogenous dopamine on binding parameters. Carbon-11-labeled raclopride was given i.v. to anaesthetised rats, positioned in a PET camera and dynamic emission scans acquired over 60 min. Time-activity curves were generated for selected regions of interest, representing striatum and cerebellum and the striatal data fitted to a compartmental model, using cerebellum as the input function, thus circumventing the need for individual metabolite-corrected plasma curves. In control rats, the binding potential (BP), defined as the ratio of the rate constants for transfer from "free to bound" and "bound to free" compartments, was of the order of 0.6. This was reduced threefold by predosing with nonradioactive raclopride. Increasing extracellular dopamine levels by predosing with d-amphetamine resulted in a significant decrease in BP whereas reducing extracellular dopamine by predosing with gamma-butyrolactone caused a significant increase. Thus, despite the limitation in spatial resolution of PET, specific binding of raclopride could be assessed from regional time-activity curves from individual rats. The system was sufficiently sensitive that changes in BP could be detected following modulation of endogenous dopamine levels, a finding of potential relevance to the interpretation of clinical PET data.     

Hemodynamic disturbances in cerebral ischemia: correlation between positron emission tomographic and angiographic findings

Proper treatment of ischemic stroke requires better understanding of cerebral hemodynamic changes. The hemodynamic changes associated with ischemia were measured using positron emission tomography and related to angiographic findings in the subacute and chronic stages of 17 ischemia patients who showed symptoms of main trunk stenosis of the internal carotid artery system. The hemodynamic factors, cerebral blood flow, cerebral blood volume, cerebral metabolic rate for oxygen, oxygen extraction fraction, and flow/volume ratio, were measured in regions of interest determined from the angiographic stenosis (over 50%) and compared in each stage. The cerebral blood flow and flow/volume ratio in the territory downstream of the main trunk stenosis and cerebral metabolic rate for oxygen in the whole cortex were decreased in the subacute stage. In the chronic stage, cerebral blood flow and flow/volume ratio decreased mainly in borderzone areas.     

A study of radiation necrosis and edema in the canine brain using positron emission tomography and magnetic resonance imaging

Evidence derived from sequence comparisons and the genomic organization of the murine Antennapedia-class homeobox gene clusters suggest that they arose from a primordial cluster through a process of gene duplication and divergence followed by cluster duplication. A large chromosomal domain surrounding the ancestral homeobox cluster also appears to have been duplicated and has remained relatively stable since the divergence of humans and rodents. To test the extent of the duplicated chromosomal domain, we have initiated physical mapping studies of the regions surrounding the four murine homeobox clusters using pulsed-field gel electrophoresis and yeast artificial chromosome cloning. In this study, we present a long-range restriction map of mouse chromosome 11 spanning 1500 kb in the region surrounding the Hox-b cluster. We have determined that the gene for the nerve growth factor receptor is tightly linked to the Hox-b complex and is located within 50 kb of the Hox-b 1 gene at the 3' end of the cluster. Four yeast artificial chromosomes have been isolated and characterized by the polymerase chain reaction, long-range restriction mapping, and Southern blotting. Two clones of 150 and 300 kb contain the entire Hox-b cluster and the nerve growth factor receptor gene. A 440-kb clone contains the 3' end of the Hox-b cluster, the nerve growth factor receptor gene, and extends downstream. A 210-kb clone contains the 5' end of the Hox-b cluster and extends upstream. These clones confirm the pulsed-field restriction map of uncloned mouse DNA and represent a contig of approximately 600 kb of cloned material from mouse chromosomes 11.     

Short-term and long-term verbal memory: a positron emission tomography study

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [15O]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.     

Cerebral blood flow and personality: a positron emission tomography study

OBJECTIVE: To determine current practice patterns of obtaining informed consent for infertility treatment by reproductive endocrinologists and to assess changes in response to reports of an association between ovulation induction and ovarian cancer. METHODS: Board-certified reproductive endocrinologists (n = 575) were surveyed by mail regarding how they informed patients and obtained consent for infertility treatments and how their practices had been influenced by studies suggesting a link between ovulation induction and ovarian cancer. Data were analyzed using chi2 and logistic regression analyses. RESULTS: The return rate was 62.1% (357 of 575 surveys). Most respondents (92%) used discussions with physicians to inform their patients of risks and benefits of all infertility treatments. Additional means, such as audiovisual aids, were used significantly more often for assisted reproductive technologies (including intracytoplasmic sperm injection and use of donated eggs) than for less invasive therapies (31-43% versus 4-11%, P < .001). Most physicians (46-66%) used verbal consent alone for hysterosalpingogram, intrauterine insemination, and ovulation induction. Formal written consent was used significantly more often for the various assisted reproductive technologies than for hysterosalpingogram, intrauterine insemination, or ovulation induction (94-95% versus 26-44%). Although most physicians (70%) did not believe that ovulation induction increases the risk of ovarian cancer, 83% addressed this risk when obtaining consent and 47% reported changing their practices since an association was reported. Common changes included limiting length of treatment and addressing ovarian cancer risk. CONCLUSION: Current practice patterns of obtaining informed consent for various infertility treatments by board-certified reproductive endocrinologists show, as expected, that informed consent is more rigorous for assisted reproductive technologies. Although most surveyed did not believe that ovulation induction increases risk of ovarian cancer, the majority of physicians addressed that risk when obtaining consent and nearly half changed their practices on the basis of a possible association.     

Abnormal brain glucose metabolism in the delusional misidentification syndromes: a positron emission tomography study in Alzheimer disease

Brain lesions have been reported with increasing frequency in the delusional misidentification syndromes (DMS). This is the first controlled study to describe DMS regional cerebral metabolic rates of glucose (rCMRglc). We compared rCMRglc (using positron emission tomography) and neuropsychological data in 9 patients with DMS and Alzheimer dementia (AD), 15 AD patients without DMS, and 17 healthy controls. The DMS group differed from the AD group without DMS in having significant hypometabolism in paralimbic (orbitofrontal and cingulate areas bilaterally) and left medial temporal areas, and significant bilateral normalized hypermetabolism in sensory association cortices (superior temporal and inferior parietal) without right left asymmetry. Compared to healthy controls, both AD groups had significant dorso lateral frontal hypometabolism bilaterally. No specific DMS neuropsychological profile was identified. Dysfunctional connections among multimodal association areas, paralimbic structures, and dorsolateral frontal cortex are proposed as the predisposing neural deficit underlying DMS, causing cognitive-perceptual-affective dissonance, which under specific conditions results in "positive" delusion formation.     

The advantage of using positron emission tomography in drug research

A large problem in drug discovery is to find relevant in vitro or in vivo animal models and to be able to extrapolate the results obtained to humans. Drug research now benefits from the fast development of imaging technologies that trace radiolabelled molecules directly in the human brain. Positron emission tomography (PET) and allied techniques use molecules that are labelled with short-lived radioisotopes and injected intravenously. The most straightforward approach is to radiolabel a new potential drug and then to trace its anatomical distribution and binding in the brain. An indirect approach is to study how the unlabelled drug inhibits specific radioligand binding. The demonstration of quantitative relationships between drug binding in vivo and drug effects in patients is used to validate targets for drug action and to optimize clinical treatment.