Publications by authors named "Thomas Opfermann"

20 Publications

  • Page 1 of 1

Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound.

Ultrasound Med Biol 2019 05 14;45(5):1243-1252. Epub 2019 Feb 14.

Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany.

Side-by-side evaluation of thyroid ultrasound (US) and TcO scintigraphy can lead to uncertainties in the correct topographic assignment of thyroid nodules. The aim of this study was to evaluate TcO single-photon emission computed tomography/ultrasound (SPECT/US) fusion imaging. Seventy-nine patients were prospectively investigated. If conventional diagnostics of the thyroid gland (B-mode-US, scintigraphy) produced unclear findings, SPECT was performed and transferred to a US device for real-time sensor-navigated 3-D fusion US investigation. The data sets were manually matched according to their contours. Finally, SPECT/US versus conventional diagnostics was rated using an ordinal 4-point scale (SPECT/US > conventional diagnostics, SPECT/US > conventional diagnostics, SPECT/US = conventional diagnostics, SPECT/US < conventional diagnostics). SPECT/US was superior (>, >) in 84% and equivalent (=) in 16% of the cases, respectively. No statistically significant differences were observed for uni-, bi- and multinodular goiters (p ≥ 0.3). In 67%, the respective problem that arose after conventional diagnostics was clarified by SPECT/US. SPECT/US was feasible and was helpful for the clarification of uncertain functionality assessments of thyroid nodules.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2019.01.003DOI Listing
May 2019

Determination of effective half-life of I in patients with differentiated thyroid carcinoma: comparison of cystatin C and creatinine-based estimation of renal function.

Endocrine 2019 03 1;63(3):554-562. Epub 2018 Nov 1.

Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany.

Purpose: Renal function and effective half-life (t) of I-131 have not been fully elucidated in patients undergoing radioiodine therapy (RAIT) for differentiated thyroid cancer (DTC). Aim of the present analysis was to evaluate the potential of cystatin C-based estimated glomerular filtration rate (eGFR) in comparison to conventional creatinine (eGFR) and to verify which methods to determine t are most accurate to predict t.

Methods: Forty-eight patients receiving whole-body I-131-scintigraphy were included. eGFR was compared to eGFR with regard to accuracy of t prediction. Three different methods (i.e. blood-based, gamma camera-based and probe-based) and two protocols with either three (short period,SP; up to 42 h) or four (long period,LP; up to 114 h) time points were compared using the Akaike's information criterion.

Results: The eGFR measurement is more likely than eGFR in predicting the t. High correlation coefficients were found between t assessed by gamma camera and probe measurements and blood-based determination revealed lower values. Patients with normal eGFR showed higher values of t of LP compared to SP.

Conclusions: eGFR should be included in further study protocols. As camera and probe measurements lead to almost superimposable results, one of the methods is expendable. Blood-based results of t were lower, presumably due to unspecific iodine retention, whereas the lower correlation with renal function may be caused by individual differences in intestinal iodine resorption. SP-protocols up to 42 h after I-131 administration are sufficient to determine t. Further studies are necessary for specific recommendations regarding I-131 activity reduction during RAIT in patients with DTC and renal insufficiency.
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http://dx.doi.org/10.1007/s12020-018-1800-4DOI Listing
March 2019

99mTc-Pertechnetate-SPECT/US Hybrid Imaging Enhances Diagnostic Certainty Compared With Conventional Thyroid Imaging With Scintigraphy and Ultrasound.

Clin Nucl Med 2018 Oct;43(10):747-748

From the Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany.

Evaluation of thyroid ultrasound and Tc-pertechnetate scintigraphy side by side frequently produces ambiguous results regarding the correct assignment of anatomy and functionality of a nodule. We describe the usefulness of Tc-pertechnetate-SPECT/US-fusion imaging. A 75-year-old woman was referred for exclusion of cold nodules. After conventional diagnostics (in vitro thyroid parameters, B mode-US, planar Tc-pertechnetate-thyroid scintigraphy), a SPECT was performed using a conventional gamma camera. The SPECT data set was transferred to an ultrasound device (LOGIQ E9), and sensor-navigated 3D ultrasound was performed. Both data sets (SPECT/US) were fused in real time, revealing the exact functional state of multiple nodules.
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http://dx.doi.org/10.1097/RLU.0000000000002241DOI Listing
October 2018

The Use of Ostrich Eggs for In Ovo Research: Making Preclinical Imaging Research Affordable and Available.

J Nucl Med 2018 12 22;59(12):1901-1906. Epub 2018 Jun 22.

Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany.

In ovo studies are a valuable option in preclinical research, but imaging studies are severely limited by the costs of dedicated equipment needed for small-sized eggs. We sought to verify the feasibility of using larger, ostrich, eggs () for imaging on the PET/CT scanners used for routine clinical investigations. Ostrich eggs were incubated until shortly before hatching, prepared for intravitelline venous injection of contrast medium or radiotracer, and imaged using native CT, contrast-enhanced CT, and PET/CT. Any technical adaptations that were needed to improve the outcome were noted. Of the 34 eggs initially incubated, 12 became fully available for imaging of embryonal development. In ovo imaging with conventional PET/CT not only was feasible but also provided images of good quality, including on dynamic PET imaging. In ovo imaging with ostrich eggs and routine clinical scanners may allow broader application of this field of preclinical research, obviating costly dedicated equipment and reducing the number of animals needed for classic animal research. Further experiments are warranted to refine this novel approach, especially to reduce motion artifacts and improve monitoring of viability.
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http://dx.doi.org/10.2967/jnumed.118.210310DOI Listing
December 2018

Radiation exposure of the investigator's hand during fusion imaging of the thyroid with 99mTcO4-free-hand SPECT and ultrasound.

Radiat Prot Dosimetry 2016 Mar 30;168(4):531-6. Epub 2015 Jul 30.

Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany Medical Engineering and Biotechnology, Jena University of Applied Sciences (EAH Jena), Jena, Germany.

The objective of this study was to assess the radiation exposure of the investigators' hand during free-hand single photon emission tomography/ultrasound ((99m)TcO4-fhSPECT/US) of the thyroid. Conventional dosimetry by rings with thermoluminescent detectors (TLDs) was performed in 32 patients (Group A), followed by TLD-chipstrate dosimetry in further 20 patients (Group B). In both the groups, the ambient dose rate was measured by dose rate meter (DRM). The applied activity was in the range of 60-80 MBq (99m)TcO4. In Group A, the exposure per investigation was 7.53 µSv (calculated average) by ring dosimetry and 9.02±5.64 µSv by DRM; in Group B, 10.93 and 9.51 ± 1.76 µSv, respectively. Based on estimated 1224 yearly thyroid investigations per nuclear medicine specialist in Germany, the estimated cumulative yearly exposure of the hand was 11.32 mSv. The hand exposure during a thyroid (99m)TcO4-fhSPECT/US of 20-min duration proved modest and comparable with different methods. Yearly examinations in excess of 1000 per investigator are not expected to add a relevant cumulative risk.
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http://dx.doi.org/10.1093/rpd/ncv375DOI Listing
March 2016

Response.

Radiology 2015 Jan;274(1):305

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January 2015

Diagnosis of de quervain's subacute thyroiditis via sensor-navigated 124Iodine PET/ultrasound (124I-PET/US) fusion.

Endocrine 2015 May 25;49(1):293-5. Epub 2014 Jul 25.

Clinic of Nuclear Medicine, Jena University Hospital, Bachstraße 18, 07743, Jena, Germany,

The role of (124)Iodine-PET/US Fusion technique is demonstrated in a 52-year-old woman with De Quervain's subacute thyroiditis. A small and adversely located lesion not detected by thyroid scintigraphy could be unambiguously matched with a hypofunctional PET finding. The presented case supports the clinical potential of PET/US Fusion technique in thyroid disease especially in small and uncertain findings.
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http://dx.doi.org/10.1007/s12020-014-0366-zDOI Listing
May 2015

18 F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis.

Arthritis Res Ther 2014 Jul 22;16(4):R155. Epub 2014 Jul 22.

Introduction: Evaluation of disease severity in experimental models of rheumatoid arthritis is inevitably associated with assessment of structural bone damage. A noninvasive imaging technology allowing objective quantification of pathophysiological alterations of bone structure in rodents could substantially extend the methods used to date in preclinical arthritis research for staging of autoimmune disease severity or efficacy of therapeutical intervention. Sodium 18 F-fluoride (18 F-NaF) is a bone-seeking tracer well-suited for molecular imaging. Therefore, we systematically examined the use of 18 F-NaF positron emission tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate isomerase (G6PI)-induced arthritis for quantification of pathological bone metabolism.

Methods: F-fluoride was injected into mice before disease onset and at various time points of progressing experimental arthritis. Radioisotope accumulation in joints in the fore- and hindpaws was analyzed by PET measurements. For validation of bone metabolism quantified by 18 F-fluoride PET, bone surface parameters of high-resolution μCT measurements were used.

Results: Before clinical arthritis onset, no distinct accumulation of 18 F-fluoride was detectable in the fore- and hindlimbs of mice immunized with G6PI. In the course of experimental autoimmune disease, 18 F-fluoride bone uptake was increased at sites of enhanced bone metabolism caused by pathophysiological processes of autoimmune disease. Moreover, 18 F-fluoride signaling at different stages of G6PI-induced arthritis was significantly correlated with the degree of bone destruction. CT enabled identification of exact localization of 18 F-fluoride signaling in bone and soft tissue.

Conclusions: The results of this study suggest that small-animal PET/CT using 18 F-fluoride as a tracer is a feasible method for quantitative assessment of pathophysiological bone metabolism in experimental arthritis. Furthermore, the possibility to perform repeated noninvasive measurements in vivo allows longitudinal study of therapeutical intervention monitoring.
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http://dx.doi.org/10.1186/ar4670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220085PMC
July 2014

Hybrid integration of real-time US and freehand SPECT: proof of concept in patients with thyroid diseases.

Radiology 2014 Jun 16;271(3):856-61. Epub 2014 Jan 16.

From the Clinic of Nuclear Medicine, Jena University Hospital, Bachstrasse 18, 07743 Jena, Germany.

Purpose: To report an initial experience regarding the feasibility and applicability of quasi-integrated freehand single photon emission computed tomography (SPECT)/ultrasonography (US) fusion imaging in patients with thyroid disease.

Materials And Methods: Local ethics committee approval was obtained, and 34 patients were examined after giving written informed consent. After intravenous application of 75 MBq of technetium 99m pertechnetate, freehand three-dimensional SPECT was performed. Data were reconstructed and transferred to a US system. The combination of two independent positioning systems enabled real-time fusion of metabolic and morphologic information during US examination. Quality of automatic coregistration was evaluated visually, and deviation was determined by measuring the distance between the center of tracer distribution and the center of the US correlate.

Results: All examinations were technically successful. For 18 of 34 examinations, the automatic coregistration and image fusion exhibited very good agreement, with no deviation. Only minor limitations in fusion offset occurred in 16 patients (mean offset ± standard deviation, 0.67 cm ± 0.3; range, 0.2-1.0 cm). SPECT artifacts occurred even in situations of clear thyroid findings (eg, unifocal autonomy).

Conclusion: The freehand SPECT/US fusion concept proved feasible and applicable; however, technical improvements are necessary.
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http://dx.doi.org/10.1148/radiol.14132415DOI Listing
June 2014

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

Clin Nucl Med 2013 Oct;38(10):770-7

From the *Clinic of Nuclear Medicine, Jena University Hospital, and †BioControl Jena, Data Analysis and Process Optimization, Jena, Germany; and ‡Spencer-Fontayne Corporation, Jersey City, NJ.

Purpose Of The Report: The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease.

Patients And Methods: Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of “hot spots” with/without central photopenia and “cold spots” detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified.

Results: 124I-PET detected significantly more “hot spots” with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more “cold spots” than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05).

Conclusions: 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.
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http://dx.doi.org/10.1097/RLU.0b013e3182a20d26DOI Listing
October 2013

Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

J Nucl Med 2013 Jun 25;54(6):848-54. Epub 2013 Mar 25.

Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany.

Unlabelled: In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice.

Methods: Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves.

Results: All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver.

Conclusion: This pilot study provided proof of principle that our simplified ED (18)F-FDG PET/CT protocol includes endpoints that effectively detect HCC hypervascularization; this finding suggests that the protocol can be used routinely.
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http://dx.doi.org/10.2967/jnumed.112.113936DOI Listing
June 2013

Insights into bone metabolism of avian embryos in ovo via 3D and 4D 18F-fluoride positron emission tomography.

Mol Imaging Biol 2012 Dec;14(6):688-98

Department of Cell and Molecular Biology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Beutenbergstr. 11a, 07745 Jena, Germany.

Purpose: The chick embryo is a well-known economical in vivo model system and is widely applied in preclinical research, e.g., bone development studies. It is therefore surprising that no studies concerning the application of (18)F-fluoride microPET to bone metabolism have been reported so far. This may be due to motion artifacts or the lack of convenient tracer injection sites.

Methods: We resolved the above problems using a combination of sample preparation, anesthesia, microPET imaging, and computational processing, and describe a convenient way of visualizing three- and four- dimensional features of bone metabolism in living chick embryos.

Results: The application of (18)F-fluoride microPET facilitates repeat measurements, highly reproducible and motion-artifact-free skeletal imaging, and provides quantitative measurements of in ovo metabolic activities in the bones of developing chick. During microPET measurement, radio tracer was injected intravascularly using a custom-made catheter system, allowing us to additionally investigate early time points in tracer kinetics and uptake.

Conclusions: Our results show that bone metabolism in living chick embryos can be reproducibly studied and quantified in ovo, even for multiple tracer injections over a longer time period. The use of dynamic (18)F-fluoride microPET imaging made it possible to visualize and analyze even small bone structures with excellent quality. Moreover, as our data are comparable to data from corresponding rodent experiments, the use of embryonated chicken eggs is a convenient and economical alternative to other animal models.
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http://dx.doi.org/10.1007/s11307-012-0550-6DOI Listing
December 2012

Detection of precursor lesions of pancreatic adenocarcinoma in PET-CT in a genetically engineered mouse model of pancreatic cancer.

Neoplasia 2011 Feb;13(2):180-6

Department of Surgery, Philipps University Marburg, Marburg, Germany.

Background: Pancreatic cancer is among the most dismal of human malignancies. The 5-year survival rate is lower than 5%. The identification of precursor lesions would be the main step to improve this fatal outcome. One precursor lesions are called pancreatic intraepithelial neoplasia (PanIN) and are graduated in grade 1 to 3, whereas grade 3 is classified as carcinoma in situ. Currently, no reliable, noninvasive imaging technique (e.g., ultrasound, computed tomography, magnet resonance imaging) exists to verify PanINs.

Methods: Recently, a transgenic mouse model of pancreatic cancer was established in which the tumor progression of human pancreatic carcinoma is reproduced. These so-called Pdx-1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+mice develop PanINs, which transform to invasive growing pancreatic carcinoma. The pancreata of mice of different ages were immunohistochemically stained using α-GLUT-2 antibodies. Furthermore, mice underwent positron emission tomography (PET)-computed tomography (CT) with (18)F-fluorodeoxyglucose (FDG) to evaluate early detection of PanIN lesions.

Results: An expression of GLUT-2 in murine PanINs was found in PanINs of grade 1B and higher. This finding is associated with an elevated glucose metabolism, leading to the detection of precursor lesions of pancreatic cancer in the FDG PET-CT scan. In addition, immunohistochemical staining of GLUT-2 was detectable in 45 (75%) of 60 human PanINs, whereas PanINs of grade 1B and higher showed a very extensive expression.

Conclusions: In conclusion, we demonstrate for the first time that an elevated glucose metabolism occurs already in precursor lesions of murine and human pancreatic carcinoma. These findings are the basis for the detection of precursor lesions by PET-CT, thereby helping improving the prognosis of this devastating disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033596PMC
http://dx.doi.org/10.1593/neo.10956DOI Listing
February 2011

Implementation of 89Zr production and in vivo imaging of B-cells in mice with 89Zr-labeled anti-B-cell antibodies by small animal PET/CT.

Appl Radiat Isot 2011 Jun 2;69(6):852-7. Epub 2011 Mar 2.

Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Germany.

We examined the production, separation, and characterization of (89)Zr, including supplementation of a commercial Cyclone(®) 18/9 with a self-made Solid Target System (STS). Obtained [(89)Zr]Zr-oxalate was used for the labeling of anti-B cell antibodies with desferrioxamine-p-SCN as a bifunctional chelator. (89)Zr-labeled antibodies were injected in DBA/1 mice to examine usability for detection of B cells in vivo. PET measurements showed binding of (89)Zr-labeled anti-B cell antibodies in tissues with high frequencies of B cells, i.e. in spleen and lymph nodes.
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http://dx.doi.org/10.1016/j.apradiso.2011.02.040DOI Listing
June 2011

In vivo molecular imaging of experimental joint inflammation by combined (18)F-FDG positron emission tomography and computed tomography.

Arthritis Res Ther 2010 3;12(6):R203. Epub 2010 Nov 3.

Institute of Immunology, Jena University Hospital, Leutragraben 3, 07743 Jena, Germany.

Introduction: The purpose of this work was to establish and validate combined small animal positron emission tomography - computed tomography (PET/CT) as a new in vivo imaging method for visualisation and quantification of joint inflammation.

Methods: Signalling of radioisotope ¹⁸F labelled Fluorodeoxyglucose (¹⁸F-FDG) injected in mice with glucose-6-phosphate isomerase (G6PI)-induced arthritis was analysed by PET/CT. Accumulation of ¹⁸F-FDG in tissue was quantified by PET measurement, whereas high definition CT delivered anatomical information. The fusion of both images revealed in detail spatial and temporal distribution and metabolism of ¹⁸F-FDG.

Results: A distinct ¹⁸F-FDG signal could be measured by PET in carpal and tarsal joints, from mice with early or established arthritis. In contrast, no accumulation of ¹⁸F-FDG was detectable before arthritis onset. Comparison of ¹⁸F-FDG joint uptake with histopathological evaluation revealed a significant correlation of both methods.

Conclusions: Small animal PET/CT using ¹⁸F-FDG is a feasible method for monitoring and, more importantly, quantitative assessment of inflammation in G6PI-arthritis. Since it is possible to perform repeated non-invasive measurements in vivo, not only numbers of animals in preclinical studies can markedly be reduced by this method, but also longitudinal studies come into reach, e. g. for individual flare-up reactions or monitoring therapy response in progressive arthritis.
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http://dx.doi.org/10.1186/ar3176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046507PMC
June 2011

Motion-artifact-free in vivo imaging utilizing narcotized avian embryos in ovo.

Mol Imaging Biol 2011 Apr;13(2):208-14

Department of Cell and Molecular Biology, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), Beutenbergstrasse 11a, 07745 Jena, Germany.

Purpose: The chick embryo in ovo is a well-accessible and economical in vivo model, but its use in molecular imaging has been limited because of motion artifacts on resulting images. The purpose of this study was to develop a method using narcotics to inhibit motility and to perform motion-artifact-free imaging of living chick embryos in ovo.

Procedures: Chick embryos in ovo were narcotized using three different narcotics: isoflurane, 2,2,2-tribromoethanol, and urethane/α-chloralose. Narcotized embryos were imaged using micro-computed tomography (microCT) at days 10-18 of incubation, and the resulting images were analyzed for reduction of motion artifacts.

Results: All three anesthetics could be used for anesthetizing living chick embryos in ovo thus allowing the acquisition of motion-artifact-free images.

Conclusions: Our experiments revealed that isoflurane is the best-suited narcotic for single and repeated applications to image living chick embryos in ovo.
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http://dx.doi.org/10.1007/s11307-010-0355-4DOI Listing
April 2011

Preferred transport of O-(2-[18F]fluoroethyl)-D-tyrosine (D-FET) into the porcine brain.

Brain Res 2007 May 9;1147:25-33. Epub 2007 Feb 9.

Institute of Physiology, University of Zurich, Switzerland.

Amino acids are valuable tracers for brain tumor imaging with positron emission tomography (PET). In this study the transport of O-(2-[(18)F]fluoroethyl)-D-tyrosine (D-FET) across the blood-brain barrier (BBB) was studied with PET in anesthetized piglets and patients after subtotal resection of brain tumors and compared with O-(2-[(18)F]fluoroethyl)-L-tyrosine (L-FET) and 3-O-methyl-6-[(18)F]fluoro-L-DOPA (L-OMFD). In piglets, compartmental modeling of PET data was used to calculate the rate constants for the blood-brain (K(1)) and the brain-blood (k(2)) transfer of D-FET, L-FET and L-OMFD. In patients standardized uptake values (SUVs) were calculated in brain cortex and lesions. Additionally, affinity determinations on various amino acid transporters (LAT1, LAT2, PAT1, XPCT) were performed in vitro using unlabeled D-FET, L-FET and L-OMFD. The initial brain uptake of D-FET in piglets was more than two-fold higher than that of l-FET, whereas the initial brain uptake of D-FET in patients was similar to that of L-FET. Calculation of K(1) and k(2) from the brain uptake curves and the plasma input data in piglets revealed about 4- and 2-fold higher values for D-FET compared to L-FET and L-OMFD, respectively. The distribution volume of D-FET in the piglet brain was slightly higher than that of L-FET as it was also found for most other organs. In brain tumor patients, initial D-FET uptake in the brain was similar to that of L-FET but showed faster tracer washout. L-FET uptake remained rather constant and provided a better delineation of residual tumor than D-FET. In conclusion, our data indicate considerable differences of stereoselective amino acid transport at the BBB in different species. Therefore, the results from animal experiments concerning BBB amino acid transport may not be transferable to humans.
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http://dx.doi.org/10.1016/j.brainres.2007.02.008DOI Listing
May 2007

Treatment with granulocyte colony-stimulating factor for mobilization of bone marrow cells in patients with acute myocardial infarction.

Am Heart J 2005 Jul;150(1):115

Klinik fuer Innere Medizin I, Friedrich-Schiller-Universitaet Jena, Jena, Germany.

Background: This study was undertaken to evaluate the hypothesis that treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize bone marrow cells (BMCs) is feasible and safe and promotes neovascularization and myocardial function in patients with acute myocardial infarction.

Methods: Fourteen patients in the treatment group and 9 patients in the control group were enrolled in this prospective, nonrandomized, open-label study. Forty-eight hours after successful recanalization and stent implantation, the patients of the treatment group received 10 microg/kg body weight per day G-CSF subcutaneously for mean treatment duration of 7.0 +/- 1.0 days. Nine patients fulfilled the entry criteria but refused participation and served therefore as control group. In both groups, regional wall motion and perfusion was evaluated with electrocardiogram-gated sestamibi single-photon emission computed tomography imaging and ejection fraction with radionuclidventriculography before discharge and after 3 months.

Results: No severe side effects of G-CSF treatment were observed. There was a significant improvement of the regional wall motion and perfusion within the treatment group (P < .0001) and between the treatment and control group (P < .05 and P < .01, respectively). Ejection fraction in the treatment group increased from 0.40 +/- 0.11 to 0.48 +/- 0.13 (P < .01), whereas in the control group, ejection fraction increased from 0.40 +/- 0.13 to 0.43 +/- 0.13 (P = .049). A control angiography of the treatment group after 12.4 +/- 6.6 months showed an in-stent restenosis in 1 patient.

Conclusion: In patients with acute myocardial infarction, treatment with G-CSF to mobilize BMCs is feasible and safe and seems to be effective under clinical conditions. The therapeutic effect might be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.
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http://dx.doi.org/10.1016/j.ahj.2005.04.030DOI Listing
July 2005

The influx of neutral amino acids into the porcine brain during development: a positron emission tomography study.

Brain Res Dev Brain Res 2004 Sep;152(2):241-53

Institute of Interdisciplinary Isotope Research Leipzig, Permoserstrasse 15, D-04318 Leipzig, Germany.

Pigs of three different age groups (newborns, 1 week old, 6 weeks old) were used to study the transport of the large neutral amino acids 6-[18F]fluoro-L-DOPA ([18F]FDOPA) and 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]OMFD) across the blood-brain barrier (BBB) with positron emission tomography (PET). Compartmental modeling of PET data was used to calculate the blood-brain clearance (K1) and the rate constant for the brain-blood transfer (k2) of [18F]FDOPA and [18F]OMFD after i.v. injection. A 40-70% decrease of K1(OMFD), K1(FDOPA) and k2(OMFD) from newborns to juvenile pigs was found whereas k2(FDOPA) did not change. Generally, K1(OMFD) and k2(OMFD) are lower than K1(FDOPA) and k2(FDOPA) in all regions and age groups. The changes cannot be explained by differences in brain perfusion because the measured regional cerebral blood flow did not show major changes during the first 6 weeks after birth. In addition, alterations in plasma amino acids cannot account for the described transport changes. In newborn and juvenile pigs, HPLC measurements were performed. Despite significant changes of single amino acids (decrease: Met, Val, Leu; increase: Tyr), the sum of large neutral amino acids transported by LAT1 remained unchanged. Furthermore, treatment with a selective inhibitor of the LAT1 transporter (BCH) reduced the blood-brain transport of [18F]FDOPA and [18F]OMFD by 35% and 32%, respectively. Additional in-vitro studies using human LAT1 reveal a much lower affinity of FDOPA compared to OMFD or L-DOPA. The data indicate that the transport system(s) for neutral amino acids underlie(s) developmental changes after birth causing a decrease of the blood-brain barrier permeability for those amino acids during brain development. It is suggested that there is no tight coupling between brain amino acid supply and the demands of protein synthesis in the brain tissue.
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http://dx.doi.org/10.1016/j.devbrainres.2004.07.002DOI Listing
September 2004