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1.
Chris Suckow Claudia Kuntner Patrick Chow Robert Silverman Arion Chatziioannou David Stout 《Molecular imaging and biology》2009,11(2):100-106
Purpose The ability to reproducibly and repeatedly image rodents in noninvasive imaging systems, such as small-animal positron emission
tomography (PET) and computed tomography (CT), requires a reliable method for anesthetizing, positioning, and heating animals
in a simple reproducible manner. In this paper, we demonstrate that mice and rats can be reproducibly and repeatedly imaged
using an imaging chamber designed to be rigidly mounted on multiple imaging systems.
Procedures Mouse and rat imaging chambers were made of acrylic plastic and aluminum. MicroCT scans were used to evaluate the positioning
reproducibility of the chambers in multimodality and longitudinal imaging studies. The ability of the chambers to maintain
mouse and rat body temperatures while anesthetized with gas anesthesia was also evaluated.
Results Both the mouse and rat imaging chambers were able to reproducibly position the animals in the imaging systems with a small
degree of error. Placement of the mouse in the mouse imaging chamber resulted in a mean distance of 0.23 mm per reference
point in multimodality studies, whereas for longitudinal studies the mean difference was 1.11 mm. The rat chamber resulted
in a mean difference of 0.46 mm in multimodality studies and a mean difference of 4.31 mm in longitudinal studies per reference
point. The chambers maintained rodent body temperatures at the set point temperature of 38°C.
Conclusions The rodent imaging chambers were able to reproducibly position rodents in tomographs with a small degree of variability and
were compatible with routine use. The embedded anesthetic line and heating system was capable of maintaining the rodent’s
temperature and anesthetic state, thereby enhancing rodent health and improving data collection reliability. 相似文献
2.
Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET. 总被引:1,自引:0,他引:1
Jens P Bankstahl Claudia Kuntner Aiman Abrahim Rudolf Karch Johann Stanek Thomas Wanek Wolfgang Wadsak Kurt Kletter Markus Müller Wolfgang L?scher Oliver Langer 《Journal of nuclear medicine》2008,49(8):1328-1335
The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. METHODS: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). RESULTS: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. CONCLUSION: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB. 相似文献
3.
Zoufal Viktoria Mairinger Severin Krohn Markus Wanek Thomas Filip Thomas Sauberer Michael Stanek Johann Traxl Alexander Schuetz John D. Kuntner Claudia Pahnke Jens Langer Oliver 《Molecular imaging and biology》2019,21(2):306-316
Molecular Imaging and Biology - Multidrug resistance-associated proteins (MRPs) mediate the hepatobiliary and renal excretion of many drugs and drug conjugates. The positron emission tomography... 相似文献
4.
5.
Claudia Kuntner 《Zeitschrift für medizinische Physik》2014,24(4):274-285
Pre-clinical positron emission tomography (PET) has evolved in the last few years from pure visualization of radiotracer uptake and distribution towards quantification of the physiological parameters. For reliable and reproducible quantification the kinetic modeling methods used to obtain relevant parameters of radiotracer tissue interaction are important. Here we present different kinetic modeling techniques with a focus on compartmental models including plasma input models and reference tissue input models. The experimental challenges off deriving the plasma input function in rodents and the effect of anesthesia are discussed. Finally, in vivo application of kinetic modeling in various areas of pre-clinical research is presented and compared to human data. 相似文献
6.
Ursula Berndt Christian Stanetty Thomas Wanek Claudia Kuntner Johann Stanek Michael Berger Martin Bauer Gjermund Henriksen Hans‐Jürgen Wester Herbert Kvaternik Peter Angelberger Christian Noe 《Journal of labelled compounds & radiopharmaceuticals》2008,51(3):137-145
This study describes the synthesis of a fluoroethylated derivative of [N‐methyl‐11C]2‐(4′‐methylaminophenyl)‐6‐hydroxybenzothiazole ([11C]6‐OH‐BTA‐1; Pittsburgh Compound B (PIB)), an already established amyloid imaging agent. The [11C]methylamino group of [11C]6‐OH‐BTA‐1 was formally replaced by a fluoroethyl group in a cold synthesis via N‐alkylation of N‐Boc‐2‐(4′‐aminophenyl)‐6‐(methoxyethoxymethoxy)benzothiazole with fluoroethyl tosylate. Subsequent deprotection gave the target compound 2‐[4′‐(2‐fluoroethyl)aminophenyl]‐6‐hydroxybenzothiazole (FBTA). In a radioligand competition assay on aggregated synthetic amyloid fibrils using N‐[3H‐methyl]6‐OH‐BTA‐1, 100 nM FBTA inhibited binding with 93 ± 1 and 83 ± 1% efficiency for Aβ1–40 and Aβ1–42, respectively. For the radiosynthesis a precursor carrying a tosylethyl moiety was prepared allowing the introduction of [18F]fluoride via nucleophilic substitution with [18F]tetra‐n‐butyl‐ammonium fluoride (TBAF). Subsequent removal of all protecting groups was performed in a one‐pot procedure followed by semi‐preparative HPLC, delivering the target compound [18F]FBTA in good radiochemical yield of 21% on average and radiochemical purity of ?98% at EOS. In vitro autoradiography on human postmortem AD brain tissue slices showed intense cortical binding of [18F]FBTA (1 nM), which was displaced in presence of 6‐OH‐BTA‐1 (1 µM). Brain up‐take was evaluated in wild‐type (wt) mice with microPET imaging. Based on these results, [18F]FBTA appears to be a suitable candidate tracer for amyloid imaging in humans. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
7.
Lartizien C Kuntner C Goertzen AL Evans AC Reilhac A 《Physics in medicine and biology》2007,52(16):4845-4862
PET-SORTEO is a Monte Carlo-based simulator that enables the fast generation of realistic PET data for the geometry of the ECAT EXACT HR+ scanner. In order to address the increasing need for simulation models of animal PET imaging systems, our aim is to adapt and configure this simulation tool for small animal PET scanners, especially for the widely distributed microPET R4 and Focus 220 systems manufactured by Siemens Preclinical Solutions. We propose a simulation model that can produce realistic rodent images in order to evaluate and optimize acquisition and reconstruction protocols. The first part of this study presents the validation of SORTEO against the geometries of the R4 and the Focus 220 systems. This validation is carried out against actual measurements performed on the R4 scanner at the Montreal Neurological Institute in Canada and on the Focus 220 system of the department of radiopharmaceuticals of the Austrian Research Center in Seibersdorf. The comparison of simulated and experimental performance measurements includes spatial resolution, energy spectra, scatter fraction and count rates. In the second part of the study, we demonstrate the ability to rapidly generate realistic whole-body radioactive distributions using the MOBY phantom and give comparative example case studies of the same rodent model simulated with PET-SORTEO for the R4 and Focus 220 systems. 相似文献
8.
Kerstin Römermann Thomas Wanek Marion Bankstahl Jens P. Bankstahl Maren Fedrowitz Markus Müller Wolfgang Löscher Claudia Kuntner Oliver Langer 《Nuclear medicine and biology》2013,40(7):873-878
IntroductionPositron emission tomography (PET) with [11C]verapamil, either in racemic form or in form of the (R)-enantiomer, has been used to measure the functional activity of the adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (Pgp) at the blood–brain barrier (BBB). There is some evidence in literature that verapamil inhibits two other ABC transporters expressed at the BBB, i.e. multidrug resistance protein 1 (MRP1) and breast cancer resistance protein (BCRP). However, previous data were obtained with micromolar concentrations of verapamil and do not necessarily reflect the transporter selectivity of verapamil at nanomolar concentrations, which are relevant for PET experiments. The aim of this study was to assess the selectivity of verapamil, in nanomolar concentrations, for Pgp over MRP1 and BCRP.MethodsConcentration equilibrium transport assays were performed with [3H]verapamil (5 nM) in cell lines expressing murine or human Pgp, human MRP1, and murine Bcrp1 or human BCRP. Paired PET scans were performed with (R)-[11C]verapamil in female FVB/N (wild-type), Mrp1(?/?), Mdr1a/b(?/?), Bcrp1(?/?) and Mdr1a/b(?/?)Bcrp1(?/?) mice, before and after Pgp inhibition with 15 mg/kg tariquidar.ResultsIn vitro transport experiments exclusively showed directed transport of [3H]verapamil in Mdr1a- and MDR1-overexpressing cells which could be inhibited by tariquidar (0.5 μM). In PET scans acquired before tariquidar administration, brain-to-blood ratio (Kb,brain) of (R)-[11C]verapamil was low in wild-type (1.3 ± 0.1), Mrp1(?/?) (1.4 ± 0.1) and Bcrp1(?/?) mice (1.8 ± 0.1) and high in Mdr1a/b(?/?) (6.9 ± 0.8) and Mdr1a/b(?/?)Bcrp1(?/?) mice (7.9 ± 0.5). In PET scans after tariquidar administration, Kb,brain was significantly increased in Pgp-expressing mice (wild-type: 5.0 ± 0.3-fold, Mrp1(?/?): 3.2 ± 0.6-fold, Bcrp1(?/?): 4.3 ± 0.1-fold) but not in Pgp knockout mice (Mdr1a/b(?/?) and Mdr1a/b(?/?)Bcrp1(?/?)).ConclusionOur combined in vitro and in vivo data demonstrate that verapamil, in nanomolar concentrations, is selectively transported by Pgp and not by MRP1 and BCRP at the BBB, which supports the use of (R)-[11C]verapamil or racemic [11C]verapamil as PET tracers of cerebral Pgp function. 相似文献
9.
Herbert Kvaternik Thomas Wanek Friedrich Hammerschmidt Ilse Zolle Reingard Aigner Claudia Kuntner 《Molecular imaging and biology》2014,16(3):317-321
Purpose
The application of radiolabelled inhibitors of cytochrome P450 enzymes is a novel approach for molecular imaging of adrenocortical masses to detect adrenal tumours. One potential tracer is radiolabelled iodometomidate (IMTO) with a common option for scintigraphic diagnosis and therapeutic applications. The aim of this study was to radiolabel iodometomidate with the positron-emitting radionuclide iodine-124 (124I) for the investigation of the biological behaviour and pharmacokinetics with positron emission tomography (PET).Procedures
[124I]IMTO has been synthesized by oxidative radioiodo-destannylation, purified via semi-preparative HPLC and formulated in acetate-buffered saline, which contained ascorbic acid and ethanol to avoid radiolytic decomposition. Biological evaluation was performed in rats which received 5.5?±?0.7 MBq [124I]IMTO in vivo. The radioactivity distribution (n?=?3) has been dynamically imaged from 0–120 min after intravenous (i.v.) injection by small-animal PET. Regions of interest have been defined manually in the reconstructed PET images, and the activity concentration was expressed as percent injected dose per gram tissue (%ID/g).Results
[124I]IMTO was prepared with a radiochemical yield of 83?±?5 % (n?=?3) and a radiochemical purity of >97 %. The final formulation of [124I]IMTO was stable for up to 48 h at room temperature. Two hours after i.v. administration in rats, radioactivity concentration in the adrenal glands were 2.1?±?0.3 %ID/g, which was sufficient to achieve highest-contrast adrenal PET images.Conclusions
In the present study, the biological characteristics of radioiodinated metomidate were evaluated. [124I]IMTO appears as an attractive PET tracer for imaging of adrenals. 相似文献10.
Claudia Kuntner Thomas Wanek Martin Hoffer Daniel Dangl Margit Hornof Herbert Kvaternik Oliver Langer 《Molecular imaging and biology》2011,13(2):222-226