[18F]Fluorination Optimisation and the Fully Automated Production of [18F]MEL050 Using a Microfluidic System

2015 ◽  
Vol 68 (1) ◽  
pp. 69 ◽  
Author(s):  
Lidia Matesic ◽  
Annukka Kallinen ◽  
Naomi A. Wyatt ◽  
Tien Q. Pham ◽  
Ivan Greguric ◽  
...  
Keyword(s):  
Continuous Flow ◽  
Solid Phase ◽  
Radiochemical Yield ◽  
Microfluidic System ◽  
Emission Tomography ◽  
Production Scale ◽  
Automated Production ◽  
Positron Emission ◽  
Automated Hplc ◽  
Positron Emission Tomography Radiotracer

The [18F]radiolabelling of the melanin-targeting positron-emission tomography radiotracer [18F]MEL050 was rapidly optimised using a commercial continuous-flow microfluidic system. The optimal [18F]fluorination incorporation conditions were then translated to production-scale experiments (35–150 GBq) suitable for preclinical imaging, complete with automated HPLC–solid phase extraction purification and formulation. [18F]MEL050 was obtained in 43 ± 10 % radiochemical yield in ~50 min.

scholarly journals Microfluidic Preparation of 89Zr-Radiolabelled Proteins by Flow Photochemistry

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 764
Author(s):  
Daniel F. Earley ◽  
Amaury Guillou ◽  
Dion van der Born ◽  
Alex J. Poot ◽  
Jason P. Holland
Keyword(s):  
Positron Emission Tomography ◽  
Human Serum Albumin ◽  
Radiochemical Purity ◽  
Flow Reactor ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Flow Process ◽  
Automated Production ◽  
Desferrioxamine B ◽  
Positron Emission

89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2 ± 1.3% (n = 3) and radiochemical purity >90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6 ± 3.6% (n = 3) with an equivalent RCP > 90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus and optimisation of the method are required before the flow process is competitive with manual reactions.

scholarly journals Microfluidic Preparation of 89Zr-Radiolabelled Proteins by Flow Photochemistry

2021 ◽  
Author(s):  
Daniel F. Earley ◽  
Amaury Guillou ◽  
Dion van der Born ◽  
Alex J. Poot ◽  
Jason P. Holland
Keyword(s):  
Positron Emission Tomography ◽  
Human Serum Albumin ◽  
Radiochemical Purity ◽  
Flow Reactor ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Flow Process ◽  
Automated Production ◽  
Desferrioxamine B ◽  
Positron Emission

89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2±1.3% (n = 3) and radiochemical purity >90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6±3.6% (n = 3) with an equivalent RCP >90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus, and optimisation of the method is required before the flow process is competitive with manual reactions.

Imaging Enterobacterales infections in patients using pathogen-specific positron emission tomography

2021 ◽  
Vol 13 (589) ◽  
pp. eabe9805
Author(s):  
Alvaro A. Ordonez ◽  
Luz M. Wintaco ◽  
Filipa Mota ◽  
Andres F. Restrepo ◽  
Camilo A. Ruiz-Bedoya ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Solid Phase ◽  
Multidrug Resistant ◽  
Sterile Inflammation ◽  
Emission Tomography ◽  
Whole Body ◽  
Hamster Model ◽  
Positron Emission ◽  
Pet Ct

Enterobacterales represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-sorbitol (18F-FDS) can selectively detect Enterobacterales infections in murine models. Here, we demonstrate that uptake of 18F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro 18F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body 18F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed Enterobacterales infection or other pathologies demonstrated that 18F-FDS PET/CT was safe, could rapidly detect and localize Enterobacterales infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of 18F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use 18F-FDS from commercially available 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) at room temperature. In a hamster model, 18F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary Klebsiella pneumoniae pneumonia—a leading cause of complications in hospitalized patients with COVID-19. These data support 18F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.

scholarly journals Detection of Apoptotic Cells in a Rabbit Model with Atherosclerosis-Like Lesions Using the Positron Emission Tomography Radiotracer [ 18 F]ML-10

2015 ◽  
Vol 14 (8) ◽  
pp. 7290.2015.00017 ◽  
Author(s):  
Fabien Hyafil ◽  
Alexy Tran-Dinh ◽  
Samuel Burg ◽  
Sébastien Leygnac ◽  
Liliane Louedec ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Rabbit Model ◽  
Emission Tomography ◽  
Apoptotic Cells ◽  
Positron Emission ◽  
Positron Emission Tomography Radiotracer

Improved synthesis and application of [11C]benzyl iodide in positron emission tomography radiotracer production

2015 ◽  
Vol 58 (8) ◽  
pp. 342-348 ◽  
Author(s):  
Aleksandra Pekošak ◽  
Ulrike Filp ◽  
Lonneke Rotteveel ◽  
Alex J. Poot ◽  
Albert D. Windhorst
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Positron Emission ◽  
Positron Emission Tomography Radiotracer

18F-Endothelin-1, a positron emission tomography (PET) radioligand for the endothelin receptor system: radiosynthesis and in vivo imaging using microPET

2002 ◽  
Vol 103 (s2002) ◽  
pp. 4S-8S ◽  
Author(s):  
Peter JOHNSTRÖM ◽  
Neil G. HARRIS ◽  
Tim D. FRYER ◽  
Olivier BARRET ◽  
John C. CLARK ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Receptor System ◽  
Endothelin 1 ◽  
Positron Emission ◽  
Pharmacokinetic Properties ◽  
Rats And Mice ◽  
Lung And Kidney

Positron emission tomography (PET) is a powerful technique with the sensitivity to image and quantify receptor-bound radioligands in vivo. Recent progress in PET scanner technology has resulted in the development of dedicated tomographs designed for small animals, with resolution that allows the delineation of discrete organs and their larger substructures in rats and mice. Our aim was to determine whether endothelin-1 (ET-1) could be labelled with 18F, and whether the resulting 18F-ET-1 would have the required pharmacokinetic properties to permit binding and imaging of ET receptors in vivo. 18F-ET-1 could be produced in a total radiochemical yield of 5.9±0.7% in 207±3min (n = 20). Specific radioactivities were in the range 220–370GBq/µmol, and the radiochemical purity of the isolated 18F-ET-1 was >95%. In vivo distribution in the rat was studied using microPET. High levels of 18F-ET-1 uptake were found in lung and kidney, whereas liver showed moderate levels of uptake. The resolution of the microPET scanner was sufficient to differentiate heterogeneous uptake in subrenal structures in the rat.

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