scholarly journals Fully-automated production of [68Ga]Ga-FAPI-46 for clinical application

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Sarah Spreckelmeyer ◽  
Matthias Balzer ◽  
Simon Poetzsch ◽  
Winfried Brenner
Keyword(s):  
Clinical Application ◽  
Radiochemical Purity ◽  
Clinical Settings ◽  
European Pharmacopoeia ◽  
Automated Production ◽  
In Vivo Detection ◽  
Positron Emission ◽  
Quality Control Parameters ◽  
Single Use

Abstract Background [68Ga]Ga-FAPI-46 is a promising radiopharmaceutical for in vivo detection of the fibroblast activation protein by positron emission tomography. Until now, the synthesis of [68Ga]Ga-FAPI-46 has been only performed manually. Our aim was to evaluate the automated synthesis of this radiopharmaceutical on two different commercially available synthesis modules in order to make the tracer readily available for clinical application. Results The synthesis of [68Ga]Ga-FAPI-46 with different amounts of precursor (10–50 μg) on the Modular Lab PharmTracer (MLPT) and Modular Lab eazy (ML eazy) from Eckert & Ziegler with a customized synthesis template and a customized single-use cassette yielded best results with 50 μg FAPI-46 for clinical multi-dose application. All relevant quality control parameters tested (e.g. sterility, stability and radiochemical purity) were in accordance with the European Pharmacopoeia. Conclusions [68Ga]Ga-FAPI-46 was successfully synthesized fully-automated on the synthesis modules Modular Lab PharmTracer and ML eazy and is, thus, available for multi-dose application in clinical settings.

scholarly journals Fully Automated Radiosynthesis of [18f]lbt999on Tracerlab Fxfn and Allinonemodules, A Pet Radiopharmaceutical for Imaging the Dopamine Transporter in Human Brain

2020 ◽  
Author(s):  
Christine Vala ◽  
Céline Mothes ◽  
Gabrielle Chicheri ◽  
Pauline Magadur ◽  
Gilles Viot ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Industrial Production ◽  
Radiochemical Purity ◽  
Acid Methyl Ester ◽  
Molar Activity ◽  
Positron Emission ◽  
Single Use ◽  
Radiochemical Yields ◽  
Pet Radiopharmaceutical

Abstract Background:Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3b-p-tolyl-8-aza-bicyclo[3.2.1]octane-2b-carboxylic acid methyl ester ([18F]LBT999) is a selective radioligand for in vivoneuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET). [18F]LBT999 has been produced on a TRACERlabFXFN for the Phase I study but forPhase III and a potent industrial production transfer, production has been also implemented on AllinOne (AIO)system requiring single use cassette. Both productions methods are reported herein. Results:Automation of [18F]LBT999radiosynthesis on FXFN was carried out in 35% yield (decay-corrected) in 65 min (n=16), with a radiochemical purity higher than 99 %and a molar activity of 158GBq/µmol at the end of synthesis. The transfer on the AIO platform followed by optimizations allowed the production of [18F]LBT999 in 32.7% yield (decay-corrected) within 48 min (n=5), with a radiochemical purity better than 98% and a molar activity in average higher to 154 GBq/µmol at the end of synthesis. Quality controls of both methods met the specification for clinical application.Conclusion:Both modules allow efficient and reproducible radiosynthesis of [18F]LBT999 with good radiochemical yields and a reasonable synthesis time.The developments made on AIO as its ability to meet pharmaceutical criteria and to more easily comply with GMP requirements make this approach as the best for a potent industrial production of the [18F]LBT999 and a future wider use.

Synthesis of a new 18F labeled porphyrin for potential application in positron emission tomography. In vivo imaging and cellular uptake

RSC Advances ◽  
2015 ◽  
Vol 5 (120) ◽  
pp. 99540-99546 ◽  
Author(s):  
Ana V. C. Simões ◽  
Sara M. A. Pinto ◽  
Mário J. F. Calvete ◽  
Célia M. F. Gomes ◽  
Nuno C. Ferreira ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Bladder Tumor ◽  
Radiochemical Purity ◽  
Cell Uptake ◽  
Emission Tomography ◽  
Human Bladder ◽  
Biodistribution Studies ◽  
Biodistribution Data ◽  
Positron Emission

Synthesis, labeling and initial biodistribution studies of a new [18F] radiolabeled meso-tetraphenylporphyrin (radiochemical purity >95%). Includes human bladder tumor cell uptake and biodistribution data.

scholarly journals Radiosynthesis and Evaluation of Cyclohexyl (5-(2-[11C-Carbonyl]acetamidobenzo[d]thiazol-6-yl)-2-Methylpyridin-3-yl)Carbamate ([11C]PK68) As a New Radioligand For Imaging Receptor-Interacting Protein 1 Kinase

2022 ◽  
Author(s):  
Tomoteru Yamasaki ◽  
Katsushi Kumata ◽  
Atsuto Hiraishi ◽  
Yiding Zhang ◽  
Hidekatsu Wakizaka ◽  
...  
Keyword(s):  
Acetyl Chloride ◽  
Radiochemical Purity ◽  
Specific Binding ◽  
Small Animal ◽  
Small Animal Pet ◽  
Interacting Protein ◽  
Molar Activity ◽  
Positron Emission ◽  
Key Enzyme

Abstract Background: Receptor-interacting protein 1 kinase (RIPK1) is a key enzyme in the regulation of cellular necroptosis. Recently, cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate (PK68, 5) has been developed as a potent inhibitor of RIPK1. Herein, we radiosynthesized [11C]PK68 as a new positron emission tomography (PET) ligand for imaging RIPK1 and evaluated its potential in vivo.Results: We synthesized [11C]PK68 by reacting amine precursor 14 with [11C]acetyl chloride. At the end of synthesis, we obtained [11C]PK68 of 1200–1790 MBq (n = 10) with >99% radiochemical purity and a molar activity of 37–99 GBq/μmol starting from 18–33 GBq of [11C]CO2. The fully automated synthesis took 30 min from the end of irradiation. In a small-animal PET study, [11C]PK68 was rapidly distributed in the liver and kidneys of healthy mice after injection, and was subsequently cleared from their bodies via hepatobiliary excretion and the intestinal reuptake pathway. Although there was no obvious specific binding of RIPK1 in the PET study, [11C]PK68 demonstrated relatively high stability in vivo, and may be used as a lead compound for further candidate development.Conclusions: In the present study, we successfully radiosynthesized [11C]PK68 and evaluated its potential in vivo. We are planning to optimize the chemical structure of [11C]PK68 and conduct further PET studies on it using pathological models.

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 Synthesis and Initial In Vivo Evaluation of [11C]AZ683 – a Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R)

2018 ◽  
Author(s):  
Sean S. Tanzey ◽  
Xia Shao ◽  
Jenelle Stauff ◽  
Janna Arteaga ◽  
Phillip Sherman ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Specific Activity ◽  
High Specific Activity ◽  
Colony Stimulating Factor ◽  
Positron Emission ◽  
New Strategy ◽  
Activity Yield ◽  
Stimulating Factor

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases and, in this paper, we report the radiosynthesis of [11C]AZ683 and initial evaluation of its use in CSF1R PET. [11C]AZ683 was synthesized by 11C-methylation of the desmethyl precursor with [11C]MeOTf in 3.0% non-corrected activity yield (based upon [11C]MeOTf), >99% radiochemical purity and high specific activity. Preliminary PET imaging with [11C]AZ683 revealed no brain uptake in rodents and nonhuman primates suggesting that [11C]AZ683 is a poor candidate for imaging neuroinflammation, but that it could still be useful for peripheral imaging of inflammation.

scholarly journals Multimodal magnetic resonance imaging predicts regional amyloid- β burden in the brain

2020 ◽  
Author(s):  
Anusha Rangarajan ◽  
Minjie Wu ◽  
Naomi Joseph ◽  
Helmet T. Karim ◽  
Charles Laymon ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Amyloid Β ◽  
Structural Mri ◽  
In Vivo Detection ◽  
Positron Emission ◽  
Large Numbers ◽  
Early Markers ◽  
Fluid Attenuated Inversion Recovery ◽  
The Brain

AbstractAlzheimer’s disease (AD) is the most common cause of dementia and identifying early markers of this disease is important for prevention and treatment strategies. Amyloid - β protein deposition is one of the earliest detectable pathological changes in AD. But in-vivo detection of amyloid - β using positron emission tomography (PET) is hampered by high cost and limited geographical accessibility. These factors can become limiting when PET is used to screen large numbers of subjects into prevention trials when only a minority are expected to be amyloid- β - positive. Structural MRI is advantageous; as it is relatively inexpensive and more accessible. Thus it could be widely used in large studies, even when frequent or repetitive imaging is necessary. We used a machine learning, pattern recognition, approach using intensity-based features from individual and combination of MR modalities (T1 weighted, T2 weighted, T2 fluid attenuated inversion recovery [FLAIR], susceptibility weighted imaging) to predict voxel-level amyloid- β in the brain. The MR- amyloid β relation was learned within each subject and generalized across subjects using subject–specific features (demographic, clinical, and summary MR features). When compared to other modalities, combination of T1-weighted, T2-weighted FLAIR, and SWI performed best in predicting the amyloid- β status as positive or negative. T2- weighted performed the best in predicting change in amyloid- β over two timepoints. Overall, our results show feasibility of amyloid- β prediction by MRI.

scholarly journals A Peptide-Based Positron Emission Tomography Probe for In Vivo Detection of Caspase Activity in Apoptotic Cells

2014 ◽  
Vol 20 (8) ◽  
pp. 2126-2135 ◽  
Author(s):  
Matthew R. Hight ◽  
Yiu-Yin Cheung ◽  
Michael L. Nickels ◽  
Eric S. Dawson ◽  
Ping Zhao ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Apoptotic Cells ◽  
Caspase Activity ◽  
In Vivo Detection ◽  
Positron Emission
Sign in / Sign up

Export Citation Format

Share Document