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1. PTM-VQA: Efficient Video Quality Assessment Leveraging Diverse PreTrained Models from the Wild

Author

Yuan, Kun, Liu, Hongbo, Li, Mading, Sun, Muyi, Sun, Ming, Gong, Jiachao, Hao, Jinhua, Zhou, Chao, and Tang, Yansong

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Video quality assessment (VQA) is a challenging problem due to the numerous factors that can affect the perceptual quality of a video, \eg, content attractiveness, distortion type, motion pattern, and level. However, annotating the Mean opinion score (MOS) for videos is expensive and time-consuming, which limits the scale of VQA datasets, and poses a significant obstacle for deep learning-based methods. In this paper, we propose a VQA method named PTM-VQA, which leverages PreTrained Models to transfer knowledge from models pretrained on various pre-tasks, enabling benefits for VQA from different aspects. Specifically, we extract features of videos from different pretrained models with frozen weights and integrate them to generate representation. Since these models possess various fields of knowledge and are often trained with labels irrelevant to quality, we propose an Intra-Consistency and Inter-Divisibility (ICID) loss to impose constraints on features extracted by multiple pretrained models. The intra-consistency constraint ensures that features extracted by different pretrained models are in the same unified quality-aware latent space, while the inter-divisibility introduces pseudo clusters based on the annotation of samples and tries to separate features of samples from different clusters. Furthermore, with a constantly growing number of pretrained models, it is crucial to determine which models to use and how to use them. To address this problem, we propose an efficient scheme to select suitable candidates. Models with better clustering performance on VQA datasets are chosen to be our candidates. Extensive experiments demonstrate the effectiveness of the proposed method., Comment: CVPR 2024, 11 pages, 4 figures, 7 tables

Published
2024

2. Reconstructed Convolution Module Based Look-Up Tables for Efficient Image Super-Resolution

Author

Liu, Guandu, Ding, Yukang, Li, Mading, Sun, Ming, Wen, Xing, and Wang, Bin

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Look-up table(LUT)-based methods have shown the great efficacy in single image super-resolution (SR) task. However, previous methods ignore the essential reason of restricted receptive field (RF) size in LUT, which is caused by the interaction of space and channel features in vanilla convolution. They can only increase the RF at the cost of linearly increasing LUT size. To enlarge RF with contained LUT sizes, we propose a novel Reconstructed Convolution(RC) module, which decouples channel-wise and spatial calculation. It can be formulated as $n^2$ 1D LUTs to maintain $n\times n$ receptive field, which is obviously smaller than $n\times n$D LUT formulated before. The LUT generated by our RC module reaches less than 1/10000 storage compared with SR-LUT baseline. The proposed Reconstructed Convolution module based LUT method, termed as RCLUT, can enlarge the RF size by 9 times than the state-of-the-art LUT-based SR method and achieve superior performance on five popular benchmark dataset. Moreover, the efficient and robust RC module can be used as a plugin to improve other LUT-based SR methods. The code is available at https://github.com/liuguandu/RC-LUT.

Published
2023

3. Quality-aware Pre-trained Models for Blind Image Quality Assessment

Author

Zhao, Kai, Yuan, Kun, Sun, Ming, Li, Mading, and Wen, Xing

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Blind image quality assessment (BIQA) aims to automatically evaluate the perceived quality of a single image, whose performance has been improved by deep learning-based methods in recent years. However, the paucity of labeled data somewhat restrains deep learning-based BIQA methods from unleashing their full potential. In this paper, we propose to solve the problem by a pretext task customized for BIQA in a self-supervised learning manner, which enables learning representations from orders of magnitude more data. To constrain the learning process, we propose a quality-aware contrastive loss based on a simple assumption: the quality of patches from a distorted image should be similar, but vary from patches from the same image with different degradations and patches from different images. Further, we improve the existing degradation process and form a degradation space with the size of roughly $2\times10^7$. After pre-trained on ImageNet using our method, models are more sensitive to image quality and perform significantly better on downstream BIQA tasks. Experimental results show that our method obtains remarkable improvements on popular BIQA datasets., Comment: Accepted by CVPR 2023

Published
2023

4. Aesthetic Photo Collage with Deep Reinforcement Learning

Author

Zhang, Mingrui, Li, Mading, Chen, Li, and Yu, Jiahao

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence
Abstract

Photo collage aims to automatically arrange multiple photos on a given canvas with high aesthetic quality. Existing methods are based mainly on handcrafted feature optimization, which cannot adequately capture high-level human aesthetic senses. Deep learning provides a promising way, but owing to the complexity of collage and lack of training data, a solution has yet to be found. In this paper, we propose a novel pipeline for automatic generation of aspect ratio specified collage and the reinforcement learning technique is introduced in collage for the first time. Inspired by manual collages, we model the collage generation as sequential decision process to adjust spatial positions, orientation angles, placement order and the global layout. To instruct the agent to improve both the overall layout and local details, the reward function is specially designed for collage, considering subjective and objective factors. To overcome the lack of training data, we pretrain our deep aesthetic network on a large scale image aesthetic dataset (CPC) for general aesthetic feature extraction and propose an attention fusion module for structural collage feature representation. We test our model against competing methods on two movie datasets and our results outperform others in aesthetic quality evaluation. Further user study is also conducted to demonstrate the effectiveness.

Published
2021

6. Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist’s perspective

Author

Torsten Kniess, Jörg Zessin, Peter Mäding, Manuela Kuchar, Oliver Kiss, and Klaus Kopka

Subjects
[18F]FMISO, [18F]fluoromisonidazole, Automated radiosynthesis, FASTlab, Medical physics. Medical radiology. Nuclear medicine, R895-920, Therapeutics. Pharmacology, RM1-950
Abstract

Abstract Background [18F]fluoromisonidazole ([18F]FMISO, 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole) is a commonly used radiotracer for imaging hypoxic conditions in cells. Since hypoxia is prevalent in solid tumors, [18F]FMISO is in clinical application for decades to explore oxygen demand in cancer cells and the resulting impact on radiotherapy and chemotherapy. Results Since the introduction of [18F]FMISO as positron emission tomography imaging agent in 1986, a variety of radiosynthesis procedures for the production of this hypoxia tracer has been developed. This paper gives a brief overview on [18F]FMISO radiosyntheses published so far from its introduction until now. From a radiopharmaceutical chemist’s perspective, different precursors, radiolabeling approaches and purification methods are discussed as well as used automated radiosynthesizers, including cassette-based and microfluidic systems. Conclusion In a GMP compliant radiosynthesis using original cassettes for FASTlab we produced [18F]FMISO in 49% radiochemical yield within 48 min with radiochemical purities > 99% and molar activities > 500 GBq/µmol. In addition, we report an easy and efficient radiosynthesis of [18F]FMISO, based on in-house prepared FASTlab cassettes, providing the radiotracer for research and preclinical purposes in good radiochemical yields (39%), high radiochemical purities (> 99%) and high molar activity (> 500 GBq/µmol) in a well-priced option.

Published
2023
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7. Progressive Spatial Recurrent Neural Network for Intra Prediction

Author

Hu, Yueyu, Yang, Wenhan, Li, Mading, and Liu, Jiaying

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Intra prediction is an important component of modern video codecs, which is able to efficiently squeeze out the spatial redundancy in video frames. With preceding pixels as the context, traditional intra prediction schemes generate linear predictions based on several predefined directions (i.e. modes) for blocks to be encoded. However, these modes are relatively simple and their predictions may fail when facing blocks with complex textures, which leads to additional bits encoding the residue. In this paper, we design a Progressive Spatial Recurrent Neural Network (PS-RNN) that learns to conduct intra prediction. Specifically, our PS-RNN consists of three spatial recurrent units and progressively generates predictions by passing information along from preceding contents to blocks to be encoded. To make our network generate predictions considering both distortion and bit-rate, we propose to use Sum of Absolute Transformed Difference (SATD) as the loss function to train PS-RNN since SATD is able to measure rate-distortion cost of encoding a residue block. Moreover, our method supports variable-block-size for intra prediction, which is more practical in real coding conditions. The proposed intra prediction scheme achieves on average 2.5% bit-rate reduction on variable-block-size settings under the same reconstruction quality compared with HEVC.

Published
2018

8. Joint Enhancement and Denoising Method via Sequential Decomposition

Author

Ren, Xutong, Li, Mading, Cheng, Wen-Huang, and Liu, Jiaying

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Many low-light enhancement methods ignore intensive noise in original images. As a result, they often simultaneously enhance the noise as well. Furthermore, extra denoising procedures adopted by most methods ruin the details. In this paper, we introduce a joint low-light enhancement and denoising strategy, aimed at obtaining well-enhanced low-light images while getting rid of the inherent noise issue simultaneously. The proposed method performs Retinex model based decomposition in a successive sequence, which sequentially estimates a piece-wise smoothed illumination and a noise-suppressed reflectance. After getting the illumination and reflectance map, we adjust the illumination layer and generate our enhancement result. In this noise-suppressed sequential decomposition process we enforce the spatial smoothness on each component and skillfully make use of weight matrices to suppress the noise and improve the contrast. Results of extensive experiments demonstrate the effectiveness and practicability of our method. It performs well for a wide variety of images, and achieves better or comparable quality compared with the state-of-the-art methods., Comment: Accepted by ISCAS 2018

Published
2018

9. Migration Processes – Challenges for German Cities

Author

Heinrich Mäding

Subjects
migration process, political challenges, population development, Urban groups. The city. Urban sociology, HT101-395
Abstract

In recent years, demographic processes have rightly attracted growing attention. In addition to the natural development of the population (with the phenomena of population decline and over aging), the various forms of migration (international and inter-regional migration, core city-periphery migration) present cities with a number of political challenges. This paper describes some of the important trends, induced problems, and options for action with regard to Germany

Published
2021
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10. MARLow: A Joint Multiplanar Autoregressive and Low-Rank Approach for Image Completion

Author

Li, Mading, Liu, Jiaying, Xiong, Zhiwei, Sun, Xiaoyan, and Guo, Zongming

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Multimedia
Abstract

In this paper, we propose a novel multiplanar autoregressive (AR) model to exploit the correlation in cross-dimensional planes of a similar patch group collected in an image, which has long been neglected by previous AR models. On that basis, we then present a joint multiplanar AR and low-rank based approach (MARLow) for image completion from random sampling, which exploits the nonlocal self-similarity within natural images more effectively. Specifically, the multiplanar AR model constraints the local stationarity in different cross-sections of the patch group, while the low-rank minimization captures the intrinsic coherence of nonlocal patches. The proposed approach can be readily extended to multichannel images (e.g. color images), by simultaneously considering the correlation in different channels. Experimental results demonstrate that the proposed approach significantly outperforms state-of-the-art methods, even if the pixel missing rate is as high as 90%., Comment: 16 pages, 9 figures

Published
2016

11. Book Review: Zimmermann, Horst; Döring, Thomas (2019): Kommunalfinanzen. Eine Einführung in die finanzwissenschaftliche Analyse der kommunalen Finanzwirtschaft. 4., überarbeitete und erweiterte Auflage Berlin: Berliner Wissenschafts-Verlag. = Schriften zur öffentlichen Verwaltung und öffentlichen Wirtschaft 244. 26 Tabellen, 22 Abbildungen, 393 Seiten

Author

Mäding Heinrich

Subjects
Cities. Urban geography, GF125, Urbanization. City and country, HT361-384
Published
2020
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12. Gleichwertige Lebensverhältnisse und Fachpolitik – explorative Beobachtungen und Überlegungen am Beispiel der aktuellen Kohlepolitik

Author

Heinrich Mäding

Subjects
Gleichwertigkeit, Fachpolitik, Kohlepolitik, Klimaschutzpolitik, Strukturstärkungsgesetz, Kohleausstiegsgesetz, Cities. Urban geography, GF125, Urbanization. City and country, HT361-384
Abstract

Ausgehend von einer Skizze des generellen raumpolitischen Ziels „Gleichwertigkeit der Lebensverhältnisse“ wird in diesem Beitrag nach dessen Stellenwert im Rahmen der aktuellen Gesetzgebung zur Kohlepolitik gefragt. Anhand der wichtigsten Dokumente (vom Bericht der Kohlekommission im Januar 2019 bis zu den abschließenden Plenarprotokollen von Bundestag und Bundesrat im Juli 2020) wird die Operationalisierung und Gewichtung des Gleichwertigkeitszieles nachverfolgt. Trotz der großen Relevanz der Kohlepolitik für die Gleichwertigkeit und der postulierten Relevanz der Gleichwertigkeit für die Kohlepolitik bleiben die Zusammenhänge begrifflich unscharf, meist implizit und kaum nachvollziehbar. Die Gleichwertigkeit tritt im politischen Prozess im Verhältnis zu klima- und energiepolitischen Argumenten deutlich zurück.

Published
2021
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14. Actions for increased yields and easier maintenance at the Tracerlab FXC-pro system in the synthesis of L-[11C]methionine

Author

Mäding, P., Zessin, J., (0000-0003-2424-3202) Kreller, M., (0000-0003-4846-1271) Kopka, K., (0000-0002-4107-3455) Knieß, T., Mäding, P., Zessin, J., (0000-0003-2424-3202) Kreller, M., (0000-0003-4846-1271) Kopka, K., and (0000-0002-4107-3455) Knieß, T.

Abstract

L-[11C]Methionine ([11C]Met) is frequently used for the diagnosis of tumours located in brain, head and neck or for tumours induced by the multiple myeloma. The radio synthesis of [11C]Met commonly starts with [11C]CO2 with subsequent transformation to [11C]CH4 followed by transfer into [11C]CH3I which is used for final labelling of the precursor L-homocystein thiolactone hydrochloride (HCTL). [1,2] By performing these steps with the TRACERLab FXC-pro System (GE HC), however, we observed inconstant radiochemical yields and high maintenance efforts especially of the absorber material used within the gas phase iodination. Accordingly, we have searched for optimization of this radio synthesis procedure.

Published
2023

15. Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist’s perspective

Author

(0000-0002-4107-3455) Knieß, T., Zessin, J., Mäding, P., (0000-0001-7329-2049) Kuchar, M., (0000-0001-7431-0026) Kiß, O., (0000-0003-4846-1271) Kopka, K., (0000-0002-4107-3455) Knieß, T., Zessin, J., Mäding, P., (0000-0001-7329-2049) Kuchar, M., (0000-0001-7431-0026) Kiß, O., and (0000-0003-4846-1271) Kopka, K.

Abstract

[18F]Fluoromisonidazole ([18F]FMISO, 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole) is a commonly used radiotracer for imaging hypoxic conditions in cells. Since hypoxia is prevalent in solid tumors, [18F]FMISO is in clinical application for decades to explore oxygen demand in cancer cells and the resulting impact on radiotherapy and chemotherapy. Since the introduction of [18F]FMISO as positron emission tomography (PET) imaging agent in 1986, a variety of radiosynthesis procedures for the production of this hypoxia tracer has been developed. This paper gives a brief overview on [18F]FMISO radiosyntheses published so far from its introduction until now. From a radiopharmaceutical chemist’s perspective, different precursors, radiolabeling approaches and purification methods are discussed as well as used automated radiosynthesizers, including cassette-based and microfluidic systems. In a GMP compliant radiosynthesis using original cassettes for FASTlab we produced [18F]FMISO in 49% radiochemical yield within 48 min with radiochemical purities >99% and molar activities >500 GBq/µmol . In addition, we report an easy and efficient radiosynthesis of [18F]FMISO, based on in-house prepared FASTlab cassettes, providing the radiotracer for research and preclinical purposes in good radiochemical yields (39%), high radiochemical purities (>99%) and high molar activity (>500 GBq/µmol) in a well-priced option.

Published
2023

17. Das SARO-Gutachten (1961): Beurteilung von Entstehung, Inhalt und Wirkung

Author

Heinrich Mäding

Subjects
SARO-report, Policy advice, Consulting demand, Resonance of advice, Guiding principle, Strategy, Cities. Urban geography, GF125, Urbanization. City and country, HT361-384
Abstract

The paper provides a historical review and appraisal of the 1961 report by the Expert Committee Responsible for Spatial Planning (SARO), which is judged to have had great significance for the start-up phase of federal spatial planning in Germany. The focus of the analysis is on a detailed evaluation of the text according to five key questions concerning its suitability as a policy advice document. Looking back to the policy advice demands of the time, the extent to which the text fulfilled the task allocated to the committee is assessed. Looking forwards, the political resonance of the text is outlined using important spatial planning documents of the years up to 1975. It is concluded that the suitability of the text for providing policy advice is limited by a number of factors. Criticisms include the use of the carrying capacity concept as a benchmark and the insufficient elaboration of the strategy in both material and procedural terms. Nonetheless, the political resonance of the document was positive and the report represented an important step towards the Spatial Planning Act of 1965.

Published
2017
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18. Actions for increased yields and easier maintenance at the Tracerlab FXC-pro system in the synthesis of L-[11C]methionine

Author

Mäding, P., Zessin, J., (0000-0003-2424-3202) Kreller, M., (0000-0003-4846-1271) Kopka, K., (0000-0002-4107-3455) Knieß, T., Mäding, P., Zessin, J., (0000-0003-2424-3202) Kreller, M., (0000-0003-4846-1271) Kopka, K., and (0000-0002-4107-3455) Knieß, T.

Abstract

L-[11C]Methionine ([11C]Met) is frequently used for the diagnosis of tumours located in brain, head and neck or for tumours induced by the multiple myeloma. The radio synthesis of [11C]Met commonly starts with [11C]CO2 with subsequent transformation to [11C]CH4 followed by transfer into [11C]CH3I which is used for final labelling of the precursor L-homocystein thiolactone hydrochloride (HCTL). [1,2] By performing these steps with the TRACERLab FXC-pro System (GE HC), however, we observed inconstant radiochemical yields and high maintenance efforts especially of the absorber material used within the gas phase iodination. Accordingly, we have searched for optimization of this radio synthesis procedure.

Published
2022

21. Rezensionen

Author

Hofmeister, Sabine, Quack, Heinz-Dieter, Deiters, Jürgen, Mäding, Heinrich, Müller, Thomas, and Wrobel, Martin

Published
2009
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23. Rezensionen

Author

Walz, Ulrich, Spannowsky, Willy, Liebe, Jana, Knopp, Lothar, and Mäding, Heinrich

Published
2007
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24. Optimierungsaspekte bei der Herstellung von L-[11C]Methionin mit dem Tracerlab FXC-pro System

Author

Mäding, P., Zessin, J., (0000-0002-4107-3455) Knieß, T., Mäding, P., Zessin, J., and (0000-0002-4107-3455) Knieß, T.

Abstract

L-[11C]Methionin ([11C]Met) ist ein oft verwendetes PET-Radiopharmakon zur Diagnose Hirn-, Kopf-, Hals- sowie vom multiplen Myelom indizierten Tumoren. Die Radiosynthese von [11C]Met ausgehend von [11C]CO2 mit dem TRACERlab FXC-pro System liefert mitunter schwankende Ausbeuten, deren Ursache unklar ist.

Published
2020

29. Rezensionen

Author

Sabine Hofmeister, Heinz-Dieter Quack, Jürgen Deiters, Heinrich Mäding, Thomas Müller, and Martin Wrobel

Subjects
Book review, Cities. Urban geography, GF125, Urbanization. City and country, HT361-384
Published
2009
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31. Rezensionen

Author

Ulrich Walz, Willy Spannowsky, Jana Liebe, Lothar Knopp, and Heinrich Mäding

Subjects
Cities. Urban geography, GF125, Urbanization. City and country, HT361-384
Published
2007
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34. Rezensionen

Author

Brigitte Adam, Robert Kaltenbrunner, and Heinrich Mäding

Subjects
Cities. Urban geography, GF125, Urbanization. City and country, HT361-384
Published
2005
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36. Umweltverträglichkeitsprüfung und Straßenbau – einige verwaltungswissenschaftliche Überlegungen

Author

Heinrich Mäding

Subjects
Cities. Urban geography, GF125, Urbanization. City and country, HT361-384
Abstract

Für die Umsetzung der EG-Richtlinie zur Umweltverträglichkeitsprüfung (UVP) ins nationale Recht sind neben fachlich-inhaltlichen Problemen der UVP verwaltungswissenschaftliche und darunter Verfahrensfragen von großer Wichtigkeit. Die “Geschichte“ der Berücksichtigung von Umweltwirkungen in der Generalplanung und in der Objektplanung für Bundesfernstraßen zeigt zwischen 1971 und 1985 deutliche Fortschritte. Bei der Objektplanung soll seit der Novellierung des Raumordnungsgesetzes 1989 das Raumordnungsverfahren die 1. Stufe der UVP enthalten. In Anlehnung an vier verfahrensmäßige Voraussetzungen für eine effektive UVP (nach Schemel) wird geprüft, inwieweit EG-Richtlinie und UVP-Gesetzentwurf hinsichtlich vertikaler Vollständigkeit, Querschnittscharakter, Unabhängigkeit vom Projektträger und Öffentlichkeitsbeteiligung über die heutige Praxis der Prüfung hinausgehen und inwieweit auch sie noch Defizite gegenüber weitergehenden Forderungen aufweisen. In diesem Zusammenhang wird u.a. vorgeschlagen. – die Umweltkosten in der Generalplanung verstärkt zu berücksichtigen, – trotz §11 UVP-Gesetzentwurf die Nützlichkeit eigenständiger UVP-Abschlußdokumente weiter zu prüfen. – die Rollenverteilung der Akteure, vor allem beim Linienbestimmungs- und Raumordnungsverfahren, differenziert neu zu bestimmen, – das Raumordnungsverfahren interaktiv als Anhörung und Erörterung zu organsieren und – die Nachvollziehbarkeit des Verfahrens zu steigern.

Published
1990
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40. Module-assisted preparation of 64Cu with high specific activity

Author

Thieme, S., Walther, M., Pietzsch, H.-J., Henniger, J., Preusche, S., Mäding, P., and Steinbach, J.

Abstract

In this work the production of 64Cu via the 64Ni(p,n)64Cu reaction with optimized conditions for low current irradiation is presented. Different target setups and cleaning steps for lowering metal contaminations in the product were applied. 64Cu with high specific activities up to 1685 GBq/µmol were produced despite low overall activity ( ~ 4.2 GBq per run). The module processing leads to a highly reproducible, reliable product quality (< 1 µg Cu and < 7 µg Ni). Beside its diagnostic value 64Cu may be of interest even for therapeutic purposes due to its decay characteristics.

Published
2012

41. 18F-labelled CCR1-receptor antagonist is not suitable for imaging of Alzheimer's disease

Author

Beuthien-Baumann, B., Holthoff, V., Mäding, P., Bergmann, R., Pawelke, B., Holl, G., Kummer, R., Kotzerke, J., and Hoff, J.

Subjects
Positron emission tomography, CCR1 receptor antagonist, Alzheimer’s disease
Abstract

Diagnosis of Alzheimer’s disease (AD) with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) relies on typical alterations of brain glucose metabolism which are, however, not disease specific. Amyloid-β imaging has not entered clinical routine yet. Post mortem histological specimen of brain tissue from AD patients revealed enhanced expression of the chemotactic cytocine receptor 1 (CCR1). Participants, methods: CCR1-antagonist ZK811460 was labeled with fluorine-18 to explore its possible use as specific diagnostic tool in AD. Tracer characterization comprising PET imaging of brain and metabolite analysis was performed in AD patients and controls. Results: Neither qualitative evaluation nor quantitative compartment analysis of PET data did show any enhanced binding of the 18F-labeled CCR1-antagonist in the brain of AD patients or controls. Conclusion: 18F-ZK811460 did not fulfill the expectation as diagnostic tracer in PET imaging of AD.

Published
2012

42. P0808 Verfahren und Anordnung zur Reinigung des Reaktionsgemisches bei der Herstellung von Radiopharmaka

Author

Füchtner, F., Mäding, P., Preusche, S., and Zessin, J.

Abstract

Die Erfindung betrifft die Herstellung von Radiopharmaka, insbesondere in Verfahren, und eine Anordnung zur Reinigung des Reaktionsgemisches bei der Herstellung von Radiopharmaka, insbesondereF-markierte Radiopharmaka, wie z. B. [F]FDOPA und [F]OMFD sowie [F]FMeMcN. Erfindungsgemäß wird zur Reinigung des Raktionsgemisches eine Vorsäule als Vorreinigungssäule, gefüllt mit RP-Material (Reversed Phase Material), zur Abtrennung des bei der Reaktion verwendeten Lösungsmittels (Matrix) bzw. unerwünschter Nebenprodukte verwendet, während die eigentliche chromatographische Trennung des Reaktionsgemisches auf einer HPLC-Säule, bevorzugt einer RP-HPLC-Säule, durchgeführt wird.

Published
2010

43. First In-Human Data of Fluorine-18 Labelled Fluoromethyl-McN5652 for In-Vivo imaging of Brain Serotonin Transporters (SERT) with PET

Author

Hesse, S., Brust, P., Mäding, P., Zessin, J., Becker, G., Patt, M., Seese, A., Sorger, D., Habermann, B., Meyer, P., Luthardt, J., Bresch, A., Steinbach, J., and Sabri, O.

Abstract

Aim: DASB is currently the most frequently applied highly selective radiotracer for visualisation and quantification of central SERT. Its use, however, is hampered by the short half‐life of carbon‐11, the moderate cortical test retest reliability, and the lack for quantifying endogenous serotonin. The aim of our study was to first apply in human the new highly SERT‐selective fluorine‐18 labelled fluoromethyl analogue of (+)‐McN5652 ([18F]FMe‐McN). Methods: The synthesis of [18F]FMe‐McN was performed according to Zessin et al. with some modifications. Briefly, the demethylated (+)‐McN5652 was reacted with bromo‐[18F]fluoromethane to yield [18F]FMe‐McN, which was purified by reversed‐phase HPLC. For in vivo human studies, five healthy volunteers (2 female, age 39±10 years) underwent dynamic PET over 120 minutes after intravenuous injection of a 90 s bolus of 298±57 MBq [18F]FMe‐McN and a static acquisition over 30 minutes 3 h p.i.. PET data were coregistered with individual MRI data set using PMOD and VOI analysis was performed. Target‐to‐background‐ratios (TB‐R, cerebellum as background structure) were compared with those of a reference data set assessed by [11C]DASB‐PET in 21 healthy subjects (11 female, 38±8 years). Results: TB‐R ([18F]FMe‐McN) displays no hemispheric differences. The values are for the frontal cortex (FC) 1.02±0.04 (right‐hand side) and 1.01±0.03 (left), for the head of caudate region (caud) 1.46±0.16 (right) and 1.50±0.15 (left) and for the raphé region 2.04±0.11. Corresponding TB‐R ([11C]DASB) are 1.10±0.07 (FC right, ANOVA p=0.05), 1.08±0.78 (FC left, 0.06), 2.14±0.21 (caud right, 0.02), 2.06±0.19 (caud left, 0.04) und 2.23±0.39 (raphé, 0.04). Visually, image quality of [11C]DASB‐PET is superior to [18F]FMe‐McN . Conclusion: Cerebral radiotracer uptake fits well with the known SERT distribution also in humans. Hence, [18F]FMe‐McN might be suitable for in vivo quantification of SERT. Despite a tendency to lower TB‐R compared to [11C]DASB, the lower standard deviation of [18F]FMe‐McN TB‐R can be advantageous with regard to test‐retest estimations in larger study cohorts. Also, labelling with fluorine‐18 allows (1) later data acquisition times, which is useful for the investigation of the tracer kinetics in brain tissue (modelling), and (2) a widespread application within a satellite concept e.g. in multicenter trials. References Zessin J, Eskola O, Brust P et al. Nucl Med Biol 2001; 28: 857‐863.

Published
2010

45. Pre-clean-up of reaction mixtures in radiopharmaceutical manufacturing by on-line solid phase extraction using HPLC

Author

Füchtner, F., Mäding, P., Preusche, S., Zessin, J., and Steinbach, J.

Abstract

Objectives: Radiopharmaceuticals are usually synthesised by reaction of simple radiolabeled compounds with a non-radioactive precursor. Afterwards the labeled precursor compound undergoes frequently a deprotection reaction. The resulting reaction mixture is often quite complex and needs HPLC purification to isolate the labeled target compound in high chemical and radiochemical purity. In some cases the composition of the reaction mixture is such complex, that an off-line solid phase extraction (SPE) step is carried out before HPLC purification to separate matrix components and/or interfering solvents. This SPE prepurification of the reaction mixture is difficult to automate and needs special hardware and solvents for rinsing and eluting the SPE cartridge. Additionally, remote controlled synthesis modules become more complex.The general aim of the present work is to develop a process, which allows the pre-cleaning of reaction mixtures from disturbing matrix components by online SPE using HPLC. In detail it results from the need to improve the radiochemical purity of [18F]FDOPA and to reduce the solvent content of dimethylformamide (DMF) during manufacturing of the serotonin transporter radioligand [18F]FMeMcN 5652. Methods: The figure shows the scheme of the HPLC hardware, whereas a pre- or guard-column is used as pre-clean-up-column (X) instead of an injection loop. The selectivity of the packing material of both columns (III & X) can be selected in accordance with the separation requirements.The process includes following steps:1. Injection valve (I) in “load position”, The reaction mixture is transferred from the reaction vessel (IX) onto the pre-clean-up-column. The diameter of the packing material of the pre-clean-up-column is in the range, which allows the feeding by gas overpressure. The disturbing matrix components are passed to waste and the target compound is retained.2. The rinsing liquid is filled into the reaction vessel and rinse out the dead volume of the pre-clean-up-column. The target compound is cleaned-up and concentrated.3. Injection valve in “inject position”, The target compound is back flushed out of the pre-clean-up-column onto the separation column (III) by the HPLC mobile phase. The finely purification takes place on the separation column. The eluate is fractionated and the target compound is collected in the common way.For the purification of [18F]FDOPA from the critical radiochemical impurity [18F]fluoride a pre-clean-up-column filled with polymer-based reversed phase (RP) material is used. The finely separation was performed on a silica-based RP column.In case of [18F]FMeMcN 5652 production the clean-up from the solvent, needed for the radiolabeling, and the finely separation is carried out on columns filled with silica-based RP materials. Results: ...........................................................................[18F]FDOPA............................[18F]FMeMcN HPLC purification method ...........................................................................[18F]Fluoride [%].....................DMF [mg/ml] ------------------------------------------------------------------------------------------------------------------------------ Injection loop.........................................................7.7 (n=93)..............................1.4 (n=5) Pre-clean-up-column............................................1.4 (n=25)..............................< 0.001 (n=4) Conclusions: Using the interlinked on-line SPE / HPLC system, reaction mixtures of radiopharmaceutical synthesis can be cleaned up and disturbing matrix components can be separated from the target compound more efficiently.

Published
2009

46. Prätherapeutisches [18F]FMISO hypoxisches Volumen ist ein signifikanter prognostischer Faktor für die lokale Tumorkontrolle nach Einzeldosisbestrahlung von FaDu-Tumoren in Nacktmäusen/Pretherapeutic [F-18]FMISO hypoxic volume is a significant prognostic factor for local tumour control after single dose radiation of FaDu- tumours in night mouse

Author

Schütze, C., Bergmann, R., Mosch, B., Yaromina, A., Zips, D., Hessel, F., Thames, H. D., Mäding, P., Kotzerke, J., Baumann, M., and Beuthien-Baumann, B.

Abstract

Hintergrund: Präklinische und klinische Untersuchungen haben gezeigt, dass das Ausmaß der prätherapeutischen Tumorhypoxie das Ergebnis einer Strahlentherapie solider Tumoren beeinflusst. Derzeit werden strahlentherapeutische Interventionen wie z.B. Dosis-Eskalation partieller hypoxischer Subvolumina untersucht. In dieser Studie wurde in einer einzelnen, in Nacktmäusen transplantierten humanen Tumorzelllinie untersucht, ob das prätherapeutische [18F]FMISO hypoxische Tumorvolumen (HV) oder die Intensität des Tracer-uptakes (maximaler Standard uptake value SUVmax) mit der lokalen Tumorkontrolle nach Einzeldosisbestrahlung korreliert. Methoden: Die hSCC Zelllinie FaDu wurde subkutan auf das rechte Hinterbein von NMRI Nacktmäusen transplantiert. 70 Tiere wurden bei einem Tumorvolumen von 165-343 mm³ in das Experiment aufgenommen. Jedes Tier erhielt am Tag 0 eine PET-Untersuchung (MicroPET® P4, CTI Molecular Imaging Inc) mit dem Hypoxie-Marker 18F]FMISO ([18F]Fluormisonidazol) unter Anästhesie. Die Auswertung erfolgte mittels 3D-regions of interest über dem Tumor (ROVER software, ABX GmbH, Radeberg, Germany). Bestimmt wurde das [18F]FMISO hypoxische Volumen (HV) und der SUVmax. Anschließend wurden die Tumoren entsprechend des medianen hypoxischen Volumens für Einzeldosisbestrahlungen mit 25 Gy oder 35 Gy unter normalem Blutfluss randomisiert. Die Einzeldosisbestrahlungen erfolgten mit 200 kV Röntgenstrahlen (0.5 mm Cu, ~ 1 Gy min-1). Der experimentelle Endpunkt war die lokale Tumorkontrolle am Tag 120 nach Bestrahlung. Ergebnisse: Die lokalen Tumorkontrollraten nach Bestrahlung mit 25 Gy waren niedriger als nach Bestrahlung mit 35 Gy (22% vs. 69%, Logrank-Test p< 0.0001). Die Spanne der HV reichte von 38-353 mm³, der Median HV betrug 112 mm³ (95%CI: 92; 128 mm³). Für Tumoren < Median HV betrug die lokale Kontrollrate 33% nach 25 Gy vs. 82% nach 35 Gy (p=0.001). In Tumoren > Median HV betrug die lokale Kontrollrate 15% nach 25 Gy vs. 53% nach 35 Gy (p=0.0005). In der multivariaten Cox-Analyse konnte nach Korrektur für Dosis und Tumorvolumeneffekte ein signifikanter Effekt des HV als kontinuierliche Variable (p=0.009) oder dichotome Variable (Stratifikation entsprechend des Median HV) (p=0.039) nachgewiesen werden. Der SUVmax war bezüglich der Prognose der Heilungswahrscheinlichkeit nicht relevant. Schlussfolgerungen: Das [18F]FMISO hypoxische Tumorvolumen ist ein signifikanter unabhängiger Prädiktor für das Ergebnis einer Bestrahlung mit hohen Einzeldosen in FaDu hSCC. Diese Ergebnisse unterstützen die Hypothese, dass ein prätherapeutisches [18F]FMISO-PET wichtige Informationen für die Verschreibung einer heterogenen Bestrahlungsdosis in hypoxischen Subvolumina individueller Tumoren liefern kann. Weitere Experimente mit anderen Tumormodellen und fraktionierter Bestrahlung sind notwendig. Gefördert im Rahmen des EU-Projektes „BioCare“ Molecular Imaging for Biologically Optimized Cancer Therapy proposal# 505785 und DFG Projekt Ba 1433.

Published
2009

47. Aspects of 6-[18F]fluoro-L-DOPA preparation: Deuterochloroform as a substitute solvent for Freon 11

Author

Füchtner, F., Zessin, J., Mäding, P., and Wüst, F.

Subjects
Freon 11 substitution, 6-[18F]fluoro-L-DOPA, electrophilic radiofluorodestannylation, deuterochloroform
Abstract

Aim: Replacement of the ecologically harmful solvent Freon 11 (CFCl3) by chloroform for the module-assisted preparation of 6-[18F]fluoro-L-DOPA based on the electrophilic radiofluorodestannylation of the precursor N-formyl-3,4-di-tert-butoxycarbonyloxy-6-(trimethylstannyl)-L-phenylalanine ethyl ester. Materials and methods: The TRACERlab Fx FDOPA module (GE Medical Systems) was used for the preparation of 6-[18F]fluoro-L-DOPA. Cyclotron-produced [18F]F2 gas (5 GBq) was passed through a cooled solution (5°C) of the stannyl precursor (45 mg) in CDCl3 (10 ml). After the [18F]fluorination step, HCl (2 ml, 6 M) was added to the solution. Then the reaction mixture was heated at 80°C for 5 min under vacuum to evaporate the chloroform. The hydrolysis to remove the protecting groups was completed by heating the closed reactor at 130°C for 8 min. After cooling to 20°C the reaction mixture was purified by HPLC with two polymer-based RP columns (PRP 1, 7 μm, 10×250 mm, Hamilton) using a solution of AcOH/AcONa (pH 4.7) as eluent. The [18F]fluoro-L-DOPA fraction was collected and sterile filtrated. Results: Three types of stabilised chloroform were tested for the radiofluorination of the precursor. Only by use of deuterochloroform stabilised with silver no significant losses of radioactivity were observed. Thus, 6 [18F]fluoro-L-DOPA purified by HPLC was obtained in decay-corrected radiochemical yields of 25±3%, ready for human use. Conclusion: CDCl3 has proved to be a convenient solvent for the module-assisted preparation of 6-[18F]fluoro-L-DOPA. In this way the use of the polluting Freon 11 can be avoided.

Published
2008

48. Factors affecting the specific activity of [18F]fluoride from a [18O]water target

Author

Füchtner, F., Preusche, S., Mäding, P., Zessin, J., and Steinbach, J.

Subjects
[18O]water target, Production of 18F, [19F]fluoride, specific activity, [18F]fluoride
Abstract

Aim: Characterisation of the influence of different polymeric tube materials of a water target system, used for the production of 18F activity, on the specific activity of radiotracers. Material, methods: Target water samples taken from different locations of the 18F water target system of a Cyclone® 18/9 cyclotron, equipped with Teflon® (PTFE) or polypropylene (PP) tubes, were analyzed for non-radioactive [19F]fluoride content. [19F]Fluoride content was measured by ion chromatography (IC20, Dinoex) with suppressed conductivity detection. Both the ion chromatographic results and the amount of 18F activity produced were used for the calculation of the specific activity (SA) of [18F]fluoride at the start of the labelling synthesis. To check these results, the SA of the labelled receptor ligand [18F]ZK811460 was also determined by using the different tubing materials. Results: Dose-exposed PTFE tubes of the target dispensing (loading) system were identified to be a major source of [19F]fluoride contamination. Conclusion: By replacing PTFE tubes of the target dispensing system with PP tubes, the content of 19F was reduced considerably resulting in an increase of SA of the radiotracer [18F]ZK811460 by factor of two.

Published
2008

49. Experimental hypoxia as a potent stimulus for radiotracer uptake in vitro: comparison of different tumor cells and primary endothelial cells

Author

Treite, F., Oswald, J., Mäding, P., Schwenzer, B., Bergmann, R., and Pietzsch, J.

Subjects
18F-FMISO, Vascular Endothelial Growth Factor, 18F-FDG
Abstract

Introduction: Hypoxia is a common feature of solid malignant tumors. The vascular endothelial growth factor (VEGF) is upregulated by hypoxia inducible factors (HIFs) as a result of central hypoxia and plays an outstanding role for the formation of new tumoral blood vessels by promoting proliferation and migration of endothelial cells. Beside [18F]fluorodeoxyglucose (18F-FDG) as standard radiotracer for tumor imaging with PET, oxygenation status in experimental and human tumors can be visualized by using [18F]fluoromisonidazole (18F-FMISO). Experimental: The aim of our study was the evaluation of the uptake of the radiotracers 18F-FDG and 18F-FMISO under standardized hypoxic conditions in various primary endothelial cells compared with three tumor cell lines in vitro. Experimental hypoxia was characterized by measurement of expression of HIF-1α, VEGF and various VEGF receptors by quantitative real-time PCR. Results and Discussion: Experimental hypoxia was confirmed by significant upregulation of characteristic hypoxia-related genes like VEGF in all analyzed primary endothelial cells and the tumor cell lines. VEGF receptors 1, 2 and 3 were almost absent in tumor cells and only expressed in endothelial cells. In contrast, the VEGF co-receptor Neuropilin-1 showed an increased expression in tumor cells under experimental hypoxia. In comparison to normoxic conditions, cellular uptake of 18F-FDG was significantly increased under experimental hypoxia in both tumor and endothelial cells. Otherwise, uptake of 18F-FMISO was always higher in tumor cells than in endothelial cells under hypoxic conditions. Conclusion: Our data showed a strong dependence of 18F-FDG uptake on the availability of oxygen in vitro. The study demonstrates relevance of endothelial cells as one important part of the tumor microenvironment under hypoxic conditions. This may have implications when performing PET studies aiming at the visualization and characterization of highly vascularized tumors, in particular, when using 18F-FDG.

Published
2007

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