Regulation of PET Radiopharmaceuticals Production in Europe

Ballinger, James R.; Koziorowski, Jacek

doi:10.1007/978-3-319-40070-9_6

Cited by 6 publications

(3 citation statements)

References 13 publications

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“…Radiochemistry optimization: improvement and simplification of the Ru-mediated 18 12) synthesis approach used in this work commercial supplier of the oxalate salt. This may hinder good manufacturing/radiopharmaceutical/clinical practice (GMP/GRPP/GCP) applications with the synthesized radiotracer as additional analytical evaluations, toxicity tests, and reliable and established production of the additive may be needed to comply with potential clinical trials in human patients [63]. As mentioned in a previous report [58], salt additives tend to reduce the 18 F-deoxyfluorination yield even though the elution efficiency is increased.…”

Section: Synthesis Of Precursors and 18 F-fluorination Strategymentioning

confidence: 98%

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

et al. 2020

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Background: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [ 18 F]Atorvastatin, the 18 Flabeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. Results: [ 18 F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18 F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [ 18 F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol −1 . Incubation of [ 18 F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [ 18 F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [ 18 F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. Conclusions: The improved ruthenium-mediated 18 F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [ 18 F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [ 18 F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.

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Section: Synthesis Of Precursors and 18 F-fluorination Strategymentioning

confidence: 98%

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

et al. 2020

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“…Both a general chapter of EP entitled "Extemporaneous Preparation of Radiopharmaceuticals" [6] and the new PIC/S guidance document with Annex 3 on radiopharmaceuticals [7] are published and worked as comprehensive guidelines for such magistral approach. Furthermore, because of the special characteristics of PET radiopharmaceuticals, the clinical studies using diagnostic radiopharmaceuticals do not fall within the GMP-compliance regulations of conventional drugs from EU Regulation no 536/2014 of 16 April 2014 [8,9]. On brief summary, no matter EP or PIC/S document, they both clearly define a clear distinction between PET radiopharmaceuticals and conventional medicine, and further provide the corresponding guidance.…”

Section: European Regulatory Viewmentioning

confidence: 99%

An Overview of PET Radiopharmaceuticals in Clinical Use: Regulatory, Quality and Pharmacopeia Monographs of the United States and Europe

Huang¹

2019

Nuclear Medicine Physics

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Since 1976, more and more PET radiopharmaceuticals have been developed as the clinical introduction of [ 18 F]FDG for various medical applications. However, few of them could be involved in routinely clinical use in hospitals partly because of restrictions in regulatory and facilities. This chapter aims to provide an overview of PET radiopharmaceuticals that are common manufactured (or prepared) in industry (or hospitals) about regulatory and quality aspects, and further summarize pharmacopeia-listed PET radiopharmaceuticals and their clinical usefulness herein. Particularly, PET radiopharmaceuticals listed in latest United States Pharmacopeia (USP) and/or European Pharmacopeia (EP) are included for this chapter. Finally, this chapter would be helpful in the basic understanding of clinical PET radiopharmaceuticals for physicians or technologists.

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“…Cell and molecular biology are very important to the future of cancer research. There have been developed different techniques of molecular biology used to study mechanisms, diagnose and treat cancer, such as: sequencing technologies, genome-editing tools, manipulation and analysis of DNA, RNA, proteins, lipids, three-dimensional culture systems, diagnostic imaging agents and radiopharmaceuticals for imaging modalities that are used in medical imaging procedures, retroviral therapy, silencing of oncogenes and mutations in tumor suppressor genes [1][2][3][4][5][6]. These approaches and tools are likely to make a major impact on both our understanding of the disease and the identification of novel therapeutic.…”

Section: Introductionmentioning

confidence: 99%

A look into the use of Raman spectroscopy for brain and breast cancer diagnostics: linear and non-linear optics in cancer research as a gateway to tumor cell identity

Abramczyk

Brożek-Płuska

Jarota

et al. 2020

Expert Review of Molecular Diagnostics

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Introduction: Currently, intensely developing of linear and non-linear optical methods for cancer detection provides a valuable tool to improve sensitivity and specificity. One of the main reasons for insufficient progress in cancer diagnostics is related to the fact that most cancer types are not only heterogeneous in their genetic composition but also reside in varying microenvironments and interact with different cell types. Until now, no technology has been fully proven for effective detecting of invasive cancer, which infiltrating the extracellular matrix. Areas covered: This review investigates the current status of Raman spectroscopy and Raman imaging for brain and breast cancer diagnostics. Moreover, the review provides a comprehensive overview of the applicability of atomic force microscopy (AFM), linear and non-linear optics in cancer research as a gateway to tumor cell identity. Expert commentary: A combination of linear and non-linear optics, particularly Raman-driven methods, has many additional advantages to identify alterations in cancer cells that are crucial for their proliferation and that distinguish them from normal cells.

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Regulation of PET Radiopharmaceuticals Production in Europe

Cited by 6 publications

References 13 publications

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

An Overview of PET Radiopharmaceuticals in Clinical Use: Regulatory, Quality and Pharmacopeia Monographs of the United States and Europe

A look into the use of Raman spectroscopy for brain and breast cancer diagnostics: linear and non-linear optics in cancer research as a gateway to tumor cell identity

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