@article{WernerWakabyashiChenetal.2018,
  author    = {Werner, Rudolf and Wakabyashi, Hiroshi and Chen, Xinyu and Hirano, Mitsuru and Shinaji, Tetsuya and Lapa, Constantin and Rowe, Steven and Javadi, Mehrbod and Higuchi, Takahiro},
  title     = {Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.203828},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161279},
  year      = {2018},
  abstract  = {Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases. Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05). Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.},
  subject      = {Nierenfunktionsst{\"o}rung},
  language  = {en}
}
@article{WernerSolnesJavadietal.2018,
  author    = {Werner, Rudolf and Solnes, Lilja and Javadi, Mehrbod and Weich, Alexander and Gorin, Michael and Pienta, Kenneth and Higuchi, Takahiro and Buck, Andreas and Pomper, Martin and Rowe, Steven and Lapa, Constantin},
  title     = {SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.206631},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161298},
  year      = {2018},
  abstract  = {Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy.},
  subject      = {Standardisierung},
  language  = {en}
}
@inproceedings{WernerChenHiranoetal.2018,
  author    = {Werner, Rudolf A. and Chen, Xinyu and Hirano, Mitsuru and Nose, Naoko and Lapa, Constantin and Javadi, Mehrbod S. and Higuchi, Takahiro},
  title     = {The Impact of Ageing on [\(^{11}\)C]meta-Hydroxyephedrine Uptake in the Rat Heart},
  series = {Journal of Nuclear Medicine},
  volume    = {59},
  booktitle = {Journal of Nuclear Medicine},
  number    = {Supplement No 1},
  issn      = {0161-5505},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162228},
  pages     = {100},
  year      = {2018},
  abstract  = {No abstract available.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@unpublished{WernerIlhanLehneretal.2018,
  author    = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.},
  title     = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  issn      = {1536-1632},
  doi       = {https://doi.org/10.1007/s11307-018-1252-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164624},
  year      = {2018},
  abstract  = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@unpublished{WernerBundschuhBundschuhetal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Javadi, Mehrbod S. and Leal, Jeffrey P. and Higuchi, Takahiro and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Lapa, Constantin and Rowe, Steven P.},
  title     = {Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.118.217588},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167788},
  year      = {2018},
  abstract  = {Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center. Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4\%) instances, three readers in 40/125 (32\%) and two observers in 27/125 (21.6\%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005). Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerWakabayashiBaueretal.2018,
  author    = {Werner, Rudolf and Wakabayashi, Hiroshi and Bauer, Jochen and Sch{\"u}tz, Claudia and Zechmeister, Christina and Hayakawa, Nobuyuki and Javadi, Mehrbod S. and Lapa, Constantin and Jahns, Roland and Erg{\"u}n, S{\"u}leyman and Jahns, Valerie and Higuchi, Takahiro},
  title     = {Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis},
  series = {European Heart Journal Cardiovascular Imaging},
  journal   = {European Heart Journal Cardiovascular Imaging},
  issn      = {2047-2404},
  doi       = {10.1093/ehjci/jey119},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165601},
  pages     = {1-8},
  year      = {2018},
  abstract  = {Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis. Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund's adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease). Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.},
  subject      = {Myokarditis},
  language  = {en}
}
@article{WernerChenMayaetal.2018,
  author    = {Werner, Rudolf A. and Chen, Xinyu and Maya, Yoshifumi and Eissler, Christoph and Hirano, Mitsuru and Nose, Naoko and Wakabayashi, Hiroshi and Lapa, Constantin and Javadi, Mehrbod S. and Higuchi, Takahiro},
  title     = {The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {11120},
  issn      = {2281-5872},
  doi       = {10.1038/s41598-018-29509-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164826},
  year      = {2018},
  abstract  = {We aimed to explore the impact of ageing on 11C-Hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (-)-metaraminol as the free base (radiochemical purity >95\%) and a wide range of specific activities (0.2-141.9 GBq/μmol) were prepared. \(^{11}\)C-HED (48.7±9.7MBq, ranged 0.2-60.4μg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (\%/min) was calculated as myocardial tissue activity at 20-30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11CHED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@unpublished{WernerAndreeJavadietal.2018,
  author    = {Werner, Rudolf A. and Andree, Christian and Javadi, Mehrbod S. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P. and Pienta, Kenneth J.},
  title     = {A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging},
  series = {Urology - The Gold Journal},
  journal   = {Urology - The Gold Journal},
  issn      = {0090-4295},
  doi       = {10.1016/j.urology.2018.03.030},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161103},
  year      = {2018},
  abstract  = {No abstract available.},
  subject      = {Virchow Node},
  language  = {en}
}
@article{WernerAndreeJavadietal.2018,
  author    = {Werner, Rudolf A. and Andree, Christian and Javadi, Mehrbod S. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P. and Pienta, Kenneth J.},
  title     = {A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging},
  series = {Urology - The Gold Journal},
  volume    = {117},
  journal   = {Urology - The Gold Journal},
  issn      = {0090-4295},
  doi       = {10.1016/j.urology.2018.03.030},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164632},
  pages     = {18-21},
  year      = {2018},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{WernerChenRoweetal.2018,
  author    = {Werner, Rudolf A. and Chen, Xinyu and Rowe, Steven P. and Lapa, Constantin and Javadi, Mehrbod S. and Higuchi, Takahiro},
  title     = {Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers},
  series = {The International Journal of Cardiovascular Imaging},
  journal   = {The International Journal of Cardiovascular Imaging},
  issn      = {1569-5794},
  doi       = {10.1007/s10554-018-1469-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169134},
  year      = {2018},
  abstract  = {The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.},
  subject      = {Positronenemissionstomografie},
  language  = {en}
}