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- Antoni, Gunnar, et al.
(författare)
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Molecular Imaging of Transporters with Positron Emission Tomography
- 2009
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Ingår i: Transporters as Targets for Drugs. - Berlin : Springer. - 3540879110 - 9783540879121 - 9783540879114 ; , s. 155-186
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Bokkapitel (refereegranskat)abstract
- Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a really useful PET ligand for NET still remains to be identified. The most promising tracer to date is (S,S)-[18F]FMeNER-D2. The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditions related to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands based on cocaine were not selective, but more recently several selective tracers such as [11C]PE2I have been characterized and shown to be suitable as PET radioligands. Although there are a large number of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when [11C]McN5652 was synthesized, that this transporter was studied using PET. New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASB and [11C]MADAM and their analogues are today the most promising ligands. The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheral and central drug–Pgp interactions, although [11C]verapamil and [18F]fluoropaclitaxel are probably restricted to use in studies of the blood–brain barrier. The vesicular monoamine transporter 2 (VMAT2) is another interesting target for diagnostic imaging and [11C]DTBZ is a promising tracer. The noninvasive imaging of transporter density as a function of disease progression or availability following interaction with blocking drugs is highlighted, including the impact on both development of new therapies and the process of developing new drugs. Although CNS-related work focusing on psychiatric disorders is the main focus of this review, other applications of PET ligands, such as diagnosis of cancer, diabetes research, and drug interactions with efflux systems, are also discussed. The use of PET especially in terms of tracer development is briefly described. Finally, it can be concluded that there is an urgent need for new, selective radioligands for the study of the transporter systems in the human brain using PET.
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| 2. |
- Ekberg, Tomas, et al.
(författare)
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Clinical impact of positron emission tomography (PET) with (18F)fluorodeoxyglucose (FDG) in head and neck tumours
- 2007
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 127:2, s. 186-193
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion. PET plays an important role in staging, on suspicion of recurrence and for detection of occult primary tumours in the head and neck. Objective: Since 1998 we have used positron emission tomography (PET) with (F-18)fluorodeoxyglucose (FDG) to assess selected patients. This procedure has often helped in making decisions on staging and treatment. Patients and methods. The case records of the first 80 patients (104 PET examinations) were studied retrospectively. Results. A total of 39 examinations were performed for staging. PET detected all primary tumours except two (stage T1), and staging was adjusted after 13%. In all, 33 PET examinations were performed on suspicion of recurrent tumour. In 52% of these PET determined further treatments; in 21% PET had a direct impact on the surgical planning. In 18 patients with metastases from an occult primary tumour, PET detected 39% of those tumours; in 22% it was the sole modality to do so. No recurrences or second primary tumours were detected when PET was used for follow-up of clinically cured patients. Results were similar when squamous cell carcinomas (SCCs) were considered alone as compared to the complete material. The mean standardized uptake value (SUV) was higher for cases deemed tumour-positive than in negative cases.
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| 3. |
- Frostfeldt, Gunnar, et al.
(författare)
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Development of myocardial microcirculation and metabolism in acute ST-elevation myocardial infarction evaluated with positron emission tomography
- 2005
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 12:1, s. 43-54
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early reperfusion is an established therapeutic objective in acute myocardial infarction (MI). The relationship of regional myocardial microcirculation and metabolism toward outcome in acute human MI is not well known.METHODS AND RESULTS: In 8 patients, positron emission tomography (PET) was performed with oxygen 15-labeled water at 3 hours, 24 hours, and 3 weeks after the start of fibrinolytic treatment, with carbon 11 acetate at 3 hours and with fluorine 18 fluorodeoxyglucose at 24 hours and 3 weeks. Absolute quantification of perfusion and water-perfusable tissue fraction (PTF), metabolic activity, and substrate extraction in 4 regions of interest was performed. Coronary angiography was performed at 24 hours. Short-term outcome at 3 weeks was evaluated by contractile reserve with dobutamine stress echocardiography and lung water measurements with PET. Early regional perfusion, PTF, and extraction and utilization of oxygen and glucose decreased closer to the infarct region ( P < .001 for all). Infarct-related oxygen utilization and extraction of oxygen and glucose were closely related to outcome ( P < .01 for all). PTF improved significantly in the infarct-related regions over time in proportion to early oxygen extraction and utilization.CONCLUSIONS: This pilot study indicates that PET might be useful in the evaluation of treatment efficacy and that restoration of oxidative metabolism is more closely related to myocardial damage recovery than perfusion in the early phase after MI.
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| 5. |
- Ivanell, Stefan, et al.
(författare)
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Analysis of numerically generated wake structures
- 2009
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Ingår i: Wind Energy. - : Wiley. - 1095-4244 .- 1099-1824. ; 1, s. 63-80
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Tidskriftsartikel (refereegranskat)abstract
- Direct numerical simulations of the Navier-Stokes equations are performed to achieve a better understanding of the behaviour of wakes generated by wind turbines. The simulations are performed by combining the in-house developed computer code EllipSys3D with the actuator-line methodology. In the actuator-line method, the blades are represented by lines along which body forces representing the loading are introduced. The body forces are determined by computing local angles of attack and using tabulated aerofoil coefficients. The advantage of using the actuator-line technique is that it is not needed to resolve blade boundary layers and instead the computational resources are devoted to simulating the dynamics of the flow structures. In the present study, approximately 5 million mesh points are used to resolve the wake structure in a 120-degree domain behind the turbine. The results from the computational fluid dynamics (CFD) simulations are evaluated and the downstream evolution of the velocity field is depicted. Special interest is given to the structure and position of the tip vortices. Further, the circulation from the wake flow field is computed and compared to the distribution of circulation on the blades.
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| 6. |
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| 7. |
- Lindhe, Örjan, et al.
(författare)
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[(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal physiology
- 2009
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:9, s. 1453-1459
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: [(11)C]Acetate (C-AC) is a general PET tracer of cellular carbon flux and useful for clinical imaging in heart disease as well as prostate cancer and other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional to blood flow in many organs. Trapping is related to organ-specific enzymatic activation and formation of [(11)C]-acetyl-CoA, the fate of which has been well characterized. Due to the logistic challenges with C-AC, 2-[(18)F]fluoroacetate (F-AC) has been proposed as a marker for prostate cancer imaging. METHOD: We evaluated the potential of F-AC as a tracer for imaging blood flow and early enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected serially in three cynomolgus monkeys and one domestic pig and scanned using PET/CT. A dynamic scan covering heart and liver was followed by repeated whole-body imaging. Kinetic patterns were compared for the myocardium, liver, blood and other organs. RESULTS: C-AC kinetics and organ distribution in both species were similar to those previously established in man. In contrast, F-AC showed prolonged blood retention, no detectable trapping in myocardium or salivary glands, rapid clearance from liver and extensive excretion to bile and urine. Massive defluorination was seen in the pig, resulting in intense skeletal activity. CONCLUSION: 2-[(18)F]Fluoroacetate cannot be regarded as a functional analogue of 1-[(11)C]acetate in normal physiology and appears to be of little use for studies of organ blood flow, intermediary metabolism or lipid synthesis.
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| 8. |
- Sandblom, Gabriel, et al.
(författare)
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Positron emission tomography with C11-acetate for tumor detection and localization in patients with prostate-specific antigen relapse after radical prostatectomy
- 2006
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Ingår i: Urology. - : Elsevier BV. - 0090-4295 .- 1527-9995. ; 67:5, s. 996-1000
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate positron emission tomography with C11-acetate as a method for detecting and localizing prostate cancer recurrence. No technique for localizing and detecting prostate cancer recurrence after biochemical relapse available today is sensitive enough to localize recurrence at a stage at which salvage radiotherapy is still curative. METHODS: Twenty patients (age 56 to 77 years) who had undergone radical prostatectomy and had an increasing prostate-specific antigen level measured on two consecutive occasions were included. In addition to the investigations usually performed when prostate cancer recurrence is suspected, they underwent positron emission tomography with C11-acetate as the marker. RESULTS: Pathologic uptake of acetate was seen in 15 (75%) of the 20 patients. In 8 of these patients, a solitary lesion was found (seven in the prostatic fossa and one at the regional lymph nodes). Multiple lesions were found in the remaining 7. False-positive uptake was seen in 3 men (15%). Additional investigations in these men revealed pathologic findings other than prostate cancer. CONCLUSIONS: Positron emission tomography with C11-acetate as marker is a promising method for early detection and localization of prostate cancer recurrence. False-positive uptake does occur.
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