| 1. |
- Antoni, Gunnar, et al.
(författare)
-
Molecular Imaging of Transporters with Positron Emission Tomography
- 2009
-
Ingår i: Transporters as Targets for Drugs. - Berlin : Springer. - 3540879110 - 9783540879121 - 9783540879114 ; , s. 155-186
-
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.
|
|
| 2. |
|
|
| 3. |
- Ivanell, Stefan, et al.
(författare)
-
Analysis of numerically generated wake structures
- 2009
-
Ingår i: Wind Energy. - : Wiley. - 1095-4244 .- 1099-1824. ; 1, s. 63-80
-
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.
|
|
| 4. |
- Lindhe, Örjan, et al.
(författare)
-
[(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal physiology
- 2009
-
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
-
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.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Sörensen, Jens
(författare)
-
State collapse and reconstruction in the periphery
- 2009
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- In the 1990s, Yugoslavia, which had once been a role model for development, became a symbol for state collapse, external intervention and post-conflict reconstruction. As a result, the country became the locus for new policies to be developed and tested. These policies are in need of scrutiny and should be examined within the social and political realities that have emerged in the region, one left with two international protectorates (Bosnia and Kosovo), unresolved state formation issues, minority concerns, ethnic, social and political polarization. The author argues that both the process of state collapse and the recent changes in aid and reconstruction policy must be interpreted within the framework of a wider transformation of the international political economy and world order. Through an in-depth analysis and critical examination of post-conflict reconstruction in Kosovo, he argues that western governments and donor agencies have built policies on conceptions and assumptions for which there is no genuine historical or contemporary economic, social or political basis in the region. This discrepancy has provided further complications which are likely to remain for years to come, as recent developments in Kosovo show.
|
|
| 8. |
- Ullmark, Gösta, et al.
(författare)
-
Bone healing of severe acetabular defects after revision arthroplasty
- 2009
-
Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 80:2, s. 179-183
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Healing of acetabular bone grafts may be difficult to assess in conventional radiographs. We used PET to analyze healing of morselized bone allografts, impacted in large osteolytic acetabular defects at revision arthroplasty. PATIENTS AND METHODS: 7 cases had a cup revision because of loosening, with repair of a segmental defect using a perforated, wide and thin plate. The osteolytic acetabulum was impacted with morselized bone allograft before cementing a polyethylene cup. [(18)F]-fluoride PET scans were used to monitor bone healing inside the graft bed 1 week, 4 weeks, and 12 months after surgery. The contralateral pelvic bone above the acetabulum was used as reference. A second group of 4 cases was analyzed for bone-forming activity in the state of mechanical loosening of an acetabular component of a THA. RESULTS: Preoperatively, the uptake was raised by 64% compared to the reference. 1 week after surgery it was increased by 77% in segmental regions, while the uptake was at the reference level in cavitary regions. After 4 months the uptake was increased by 91% in cavitary regions and by 117% in segmental regions. 1 year after surgery, the increase in uptake was 20% in both regions. All implants were stable on radiographs. INTERPRETATION: We found PET to be a sensitive and useful method for evaluation of the spatial and temporal development of bone formation.
|
|
| 9. |
- Ullmark, Gösta, et al.
(författare)
-
Osteonecrosis following resurfacing arthroplasty : A clinical positron emission tomography study of 14 cases
- 2009
-
Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 80:6, s. 670-674
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: One of the main concerns regarding resurfacing arthroplasty is the viability of the remaining part of the femoral head, and the postoperative risk of a femoral neck fracture or collapse. In contrast to radiographic methods, positron emission tomography using the radiotracer [18F]-fluoride (Fluoride-PET) enables us to visualize the viability of bone in the remaining part of the head, despite the presence of the covering metal component. PATIENTS AND METHODS: This is preliminary prospective study of 14 patients who underwent an ASR resurfacing arthroplasty. Apart from clinical and radiographic analyses, all patients were analyzed by PET scan 1 week, 4 months, and 1 year after surgery. RESULTS: 1 patient had a minor region of osteonecrosis on PET scan at 1 week and at 4 months. After 1 year, the necrosis had increased to include most of the head. 2 other patients, normal at 4 months, had developed equally large osteonecrosis at 1 year. A fourth patient had a minor osteonecrosis at 1 year. None of the patients had clinical symptoms, and the necrotic areas were not visible on plain radiographs. CONCLUSIONS: We found Fluoride PET to be a sensitive and useful method for evaluation of bone metabolism at resurfacing arthroplasty. 3 of the 14 patients had developed osteonecrosis, involving most of the head at 1 year. The late onset of the phenomenon does not support the hypothesis of surgically damaged vascularity. The presence of this complication together with the lack of visibility on plain radiographs gives reason for concern.
|
|
