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  • Tovedal, Thomas, et al. (författare)
  • Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion
  • 2017
  • Ingår i: Annals of Thoracic Surgery. - 0003-4975 .- 1552-6259. ; 103:2, s. 610-616
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Perfusion strategies during aortic surgery usually comprise hypothermic circulatory arrest (HCA), often combined with selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion. Cerebral blood flow (CBF) is a fundamental parameter for which the optimal level has not been clearly defined. We sought to determine the CBF at a pump flow level of 6 mL/kg/min, previously shown likely to provide adequate SACP at 20°C in pigs.</p><p><strong>METHODS:</strong> Repeated positron emission tomography (PET) scans were used to quantify the CBF and glucose metabolism throughout HCA and SACP including cooling and rewarming. Eight pigs on cardiopulmonary bypass were assigned to either HCA alone (n = 4) or HCA+SACP (n = 4). The CBF was measured by repeated [(15)O]water PET scans from baseline to rewarming. The cerebral glucose metabolism was examined by [(18)F]fluorodeoxyglucose PET scans after rewarming to 37°C.</p><p><strong>RESULTS:</strong> Cooling to 20°C decreased the cortical CBF from 0.31 ± 0.06 at baseline to 0.10 ± 0.02 mL/cm(3)/min (p = 0.008). The CBF was maintained stable by SACP of 6 mL/kg/min during 45 minutes. After rewarming to 37°C, the mean CBF increased to 0.24 ± 0.07 mL/cm(3)/min, without significant differences between the groups at any time-point exclusive of the HCA period. The net cortical uptake (Ki) of [(18)F]fluorodeoxyglucose after rewarming showed no significant difference between the groups.</p><p><strong>CONCLUSIONS:</strong> Cooling autoregulated the CBF to 0.10 mL/cm(3)/min, and 45 minutes of SACP at 6 mL/kg/min maintained the CBF in the present model. Cerebral glucose metabolism after rewarming was similar in the study groups.</p>
  • Varasteh, Zohreh, et al. (författare)
  • In Vitro and In Vivo Evaluation of a F-18-Labeled High Affinity NOTA Conjugated Bombesin Antagonist as a PET Ligand for GRPR-Targeted Tumor Imaging
  • 2013
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 8:12, s. e81932
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Expression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer suggests that this receptor can be used as a potential molecular target to visualize and treat these tumors. We have previously investigated an antagonist analog of bombesin (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26) conjugated to 1,4,7-triazacyclononane-N,N',N ''-triacetic acid (NOTA) via a diethylene glycol (PEG(2)) spacer (NOTA-P2-RM26) labeled with Ga-68 and In-111. We found that this conjugate has favorable properties for in vivo imaging of GRPR-expression. The focus of this study was to develop a F-18-labelled PET agent to visualize GRPR. NOTA-P2-RM26 was labeled with F-18 using aluminum-fluoride chelation. Stability, in vitro binding specificity and cellular processing tests were performed. The inhibition efficiency (IC50) of the [F-nat]AlF-NOTA-P2-RM26 was compared to that of the Ga-nat-loaded peptide using I-125-Tyr(4)-BBN as the displacement radioligand. The pharmacokinetics and in vivo binding specificity of the compound were studied. NOTA-P2-RM26 was labeled with F-18 within 1 h (60-65% decay corrected radiochemical yield, 55 GBq/mu mol). The radiopeptide was stable in murine serum and showed high specific binding to PC-3 cells. [F-nat]AlF-NOTA-P2-RM26 showed a low nanomolar inhibition efficiency (IC50=4.4 +/- 0.8 nM). The internalization rate of the tracer was low. Less than 14% of the cell-bound radioactivity was internalized after 4 h. The biodistribution of [F-18]AlF-NOTA-P2-RM26 demonstrated rapid blood clearance, low liver uptake and low kidney retention. The tumor uptake at 3 h p. i. was 5.5 +/- 0.7 % ID/g, and the tumor-to-blood, -muscle and -bone ratios were 87 +/- 42, 159 +/- 47, 38 +/- 16, respectively. The uptake in tumors, pancreas and other GRPR-expressing organs was significantly reduced when excess amount of non-labeled peptide was co-injected. The low uptake in bone suggests a high in vivo stability of the Al-F bond. High contrast PET image was obtained 3 h p. i. The initial biological results suggest that [F-18]AlF-NOTA-P2-RM26 is a promising candidate for PET imaging of GRPR in vivo.</p>
  • Aarnio, Mikko, et al. (författare)
  • Evaluation of  PET tracers [<sup>11</sup>C]D-deprenyl, [<sup>11</sup>C]L-dideuteriumdeprenyl and [<sup>18</sup>F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • <p><strong>Purpose: </strong>Positron emission tomography with the radioligand [<sup>11</sup>C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whiplash injury, but the mechanism of this tracer uptake and its exact binding site in inflammation or tissue injury is still unclear. The aim of this study was to further evaluate [<sup>11</sup>C]D-deprenyl´s usefulness as a marker of acute inflammation.</p><p><strong>Methods:</strong> An animal PET/CT study was performed three days after the induction of a rat model of inflammatory or surgical pain<strong>. </strong>Fourteen adult male Sprague-Dawley rats and three tracers [<sup>11</sup>C]D-deprenyl, [<sup>11</sup>C]L-dideuterumdeprenyl and [<sup>18</sup>F]fluorodeoxyglucose were used. <strong></strong></p><p><strong>Results:</strong> No [<sup>11</sup>C]D-deprenyl accumulation was seen in a rat model of musculoskeletal pain. In the rat model of inflammatory pain all three ligands were shown to visualize the inflamed ankle joint with much lower uptake in the control ankle joint. The uptake was largest with [<sup>11</sup>C]D-deprenyl and [<sup>11</sup>C]L- dideuteriumdeprenyl, where approximately 1 % of the injected dose could be found in the affected ankle joint during the first minutes, whereas the uptake of [<sup>18</sup>F]FDG was approximately 0.5 % of the injected dose. However, the ratio of uptake of the injected ankle joint versus the control ankle joint was much higher for [<sup>18</sup>F]FDG (around 10 fold increase) than for the two deprenyl enantiomers (2 – 3 fold increase). The uptake pattern of [<sup>11</sup>C]D-deprenyl and [<sup>11</sup>C]L-dideuteriumdeprenyl did not show signs of specific binding or irreversible trapping.</p><p><strong>Conclusions:</strong> Contrary to our expectations, of the three tracers only [<sup>18</sup>F]FDG may be used as markers of peripheral inflammation in a rat model of inflammatory pain. However, as a high site-specificity is required, [<sup>11</sup>C]D-deprenyl and [<sup>11</sup>C]L-dideyteriumdeprenyl deserve further exploration regarding sensitivity, specificity and uptake mechanisms in human pain syndromes.</p>
  • Andersen, Thomas L., et al. (författare)
  • Efficient C-11-Carbonylation of Isolated Aryl Palladium Complexes for PET : Application to Challenging Radiopharmaceutical Synthesis
  • 2015
  • Ingår i: Journal of the American Chemical Society. - 0002-7863 .- 1520-5126. ; 137:4, s. 1548-1555
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with (CO)-C-11 to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first C-11-carbonyl labeling of an approved PET tracer, [C-11]raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [C-11]olaparib and [C-11]JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other C-11-labeling strategies.</p>
  • Antoni, Gunnar (författare)
  • Development of carbon-11 labelled PET tracers-radiochemical and technological challenges in a historic perspective
  • 2015
  • Ingår i: Journal of labelled compounds & radiopharmaceuticals. - 0362-4803 .- 1099-1344. ; 58:3, s. 65-72
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The development of positron emission tomography (PET) from being an exclusive and expensive research tool at major research institutes to a clinically useful modality found at most major hospitals around the world is largely dependent on radiochemistry and synthesis technology achievements by a few pioneer researchers starting their PET careers 40 to 50years ago. Especially, the introduction of [C-11]methyl iodide resulted in a quantum jump in the history of PET tracer development enabling the smooth labelling of a multitude of useful tracers. A more recent and still challenging methodological improvement is transition metal mediated C-11-carbonylations, having a large synthetic potential that has, however, not yet been realized in the clinical setting. This mini-review focuses on the history of carbon-11 radiochemistry and related technology developments and the role this played in PET tracer developments, especially emphasizing radiolabelling of endogenous compounds. A few examples will be presented of how the use of radiolabelled endogenous substances have provided fundamental information of in vivo biochemistry using the concept of position-specific labelling in different positions in the same molecule.</p>
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