Preparation of [18F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters

Patt, Marianne; Kuntzsch, Matthias; Machulla, Hans-Juergen

doi:10.1007/bf02349874

Cited by 28 publications

(6 citation statements)

References 9 publications

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“…18 F-FAZA and 18 F-FMISO were synthesized as previously described (16,17). In both cases, the synthesizer TRACERlab FXF-N (GE Healthcare) was used.…”

Section: Radiopharmaceuticalsmentioning

confidence: 99%

In Vivo Hypoxia PET Imaging Quantifies the Severity of Arthritic Joint Inflammation in Line with Overexpression of Hypoxia-Inducible Factor and Enhanced Reactive Oxygen Species Generation

et al. 2017

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Hypoxia is essential for the development of autoimmune diseases such as rheumatoid arthritis (RA) and is associated with the expression of reactive oxygen species (ROS), because of the enhanced infiltration of immune cells. The aim of this study was to demonstrate the feasibility of measuring hypoxia noninvasively in vivo in arthritic ankles with PET/MRI using the hypoxia tracers F-fluoromisonidazole (F-FMISO) and F-fluoroazomycinarabinoside (F-FAZA). Additionally, we quantified the temporal dynamics of hypoxia and ROS stress using L-012, an ROS-sensitive chemiluminescence optical imaging probe, and analyzed the expression of hypoxia-inducible factors (HIFs). Mice underwent noninvasive in vivo PET/MRI to measure hypoxia or optical imaging to analyze ROS expression. Additionally, we performed ex vivo pimonidazole-/HIF-1α immunohistochemistry and HIF-1α/2α Western blot/messenger RNA analysis of inflamed and healthy ankles to confirm our in vivo results. Mice diseased from experimental RA exhibited a 3-fold enhancement in hypoxia tracer uptake, even in the early disease stages, and a 45-fold elevation in ROS expression in inflamed ankles compared with the ankles of healthy controls. We further found strong correlations of our noninvasive in vivo hypoxia PET data with pimonidazole and expression of HIF-1α in arthritic ankles. The strongest hypoxia tracer uptake was observed as soon as day 3, whereas the most pronounced ROS stress was evident on day 6 after the onset of experimental RA, indicating that tissue hypoxia can precede ROS stress in RA. Collectively, for the first time to our knowledge, we have demonstrated that the noninvasive measurement of hypoxia in inflammation usingF-FAZA and F-FMISO PET imaging represents a promising new tool for uncovering and monitoring rheumatic inflammation in vivo. Further, because hypoxic inflamed tissues are associated with the overexpression of HIFs, specific inhibition of HIFs might represent a new powerful treatment strategy.

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“…18 F-FAZA and 18 F-FMISO were synthesized as previously described (16,17). In both cases, the synthesizer TRACERlab FXF-N (GE Healthcare) was used.…”

Section: Radiopharmaceuticalsmentioning

confidence: 99%

In Vivo Hypoxia PET Imaging Quantifies the Severity of Arthritic Joint Inflammation in Line with Overexpression of Hypoxia-Inducible Factor and Enhanced Reactive Oxygen Species Generation

et al. 2017

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“…Patt et al (1999) reported that the radiochemical yield of FMISO was dependent mainly on the amount of precursor and on the labeling reaction temperature. The HPLC purification gave higher corrected radiochemical yield of FMISO than Sep Paks purification; however, the most well-recognized limitation of HPLC purification had difficulty in performing a fully automated synthesis of PET tracers.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 18F-fluoromisonidazole Tracer for Positron Emission Tomography

Tang

2008

Cancer Imaging

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“…On-chip radiochemistry requires material compatibility to commonly used aggressive media such as hydrochloric acid (HCl), sodium hydroxide (NaOH), or solvents like dimethyl sulfoxide (DMSO), acetonitrile (MeCN), dimethylformamide (DMF) and ethanol (EtOH), for example. Depending on the specific PET tracer to be synthesized, required process temperatures range from –20 °C for e.g., carbon-11 chemistries [64], 20 °C for e.g., fluoride-18 radiolabeling of peptides [65], 110 °C for common PET tracers such as [ 18 F]FDG [17] or [ 18 F]fluoromisonidazol ([ 18 F]FMISO) [66] and 160 °C for compounds such as [ 18 F]FLT [18]. Recent results on microfluidic [ 18 F]FLT synthesis suggest that the use of decreased reaction temperatures due to improved heat transfer in micro-scale systems is possible [67].…”

Section: Functional Elementsmentioning

confidence: 99%

Microfluidics: A Groundbreaking Technology for PET Tracer Production?

Rensch¹,

Jackson²,

Lindner

et al. 2013

Molecules

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Application of microfluidics to Positron Emission Tomography (PET) tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state OPEN ACCESSMolecules 2013, 18 7931 of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch-and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed.

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Preparation of [18F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters

Cited by 28 publications

References 9 publications

In Vivo Hypoxia PET Imaging Quantifies the Severity of Arthritic Joint Inflammation in Line with Overexpression of Hypoxia-Inducible Factor and Enhanced Reactive Oxygen Species Generation

In Vivo Hypoxia PET Imaging Quantifies the Severity of Arthritic Joint Inflammation in Line with Overexpression of Hypoxia-Inducible Factor and Enhanced Reactive Oxygen Species Generation

Synthesis of 18F-fluoromisonidazole Tracer for Positron Emission Tomography

Microfluidics: A Groundbreaking Technology for PET Tracer Production?

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