A simplified radiometabolite analysis procedure for PET radioligands using a solid phase extraction with micellar medium

Nakao, Ryuji; Halldin, Christer

doi:10.1016/j.nucmedbio.2013.02.007

Cited by 4 publications

(4 citation statements)

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“…However, this method suffers from high back pressure as it is required a large plasma volume for radiometabolite analysis. Nakao et al have developed an alternative rapid and efficient method based on micellar liquid chromatography for the direct analysis of plasma radiometabolites [24,38,46]. This method uses micellar/high submicellar liquid chromatography along with semi-preparative alkyl-bonded silica column for the analysis of radiometabolites.…”

Section: Methods Of Radiometabolite Analysismentioning

confidence: 99%

“…Identification of radiometabolites during the evolution of a new radiotracer is also important as it offers information about the most suitable position to radiolabel a compound to escape any production of inquisitive radiometabolites [22,23]. There are some reviews already published on PET radiometabolites [24,25]. However, those reviews mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process.…”

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confidence: 99%

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Dealing with PET radiometabolites

et al. 2020

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Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer’s fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging. Graphical abstract

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Section: Methods Of Radiometabolite Analysismentioning

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Dealing with PET radiometabolites

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“…The radioactivity of plasma and the protein precipitate fraction was measured to quantify the recovery after precipitation with acetonitrile. The portion of unchanged [ 11 C]PBR28 was estimated after correcting for the precipitate radioactivity because its radiometabolites tend to bind to the protein precipitate after addition of acetonitrile …”

Section: Methodsmentioning

confidence: 99%

“…The portion of unchanged [ 11 C]PBR28 was estimated after correcting for the precipitate radioactivity because its radiometabolites tend to bind to the protein precipitate after addition of acetonitrile. 24 In the ultrafiltration method, human plasma (500 μL) taken 5 min before administration was mixed with the [ 11 C]PBR28 solution (50 μL, approximately 20 MBq) and incubated at room temperature for 10 min. A 200 μL portion of the incubation mixture was pipetted into an ultrafiltration tube (Centrifree YM-30, cutoff 30 000 MW, Millipore) and centrifuged at 1500g for 15 min.…”

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Simultaneous Determination of Protein-Free and Total Positron Emission Tomography Radioligand Concentrations in Plasma Using High-Performance Frontal Analysis Followed by Mixed Micellar Liquid Chromatography: Application to [¹¹C]PBR28 in Human Plasma

2013

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A two-dimensional liquid chromatographic (LC) system was developed for the determination of protein-free and total (free + bound forms) positron emission tomography (PET) radioligand concentrations in plasma by direct plasma injection. The unbound PET radioligand was first analyzed by high-performance frontal analysis using a short gel-filtration column and phosphate buffered saline solution as the mobile phase. All the collected effluent from the gel-filtration column was then transferred to the second dimension consisting of a monolithic C-18 column and mixed (anionic and nonionic surfactants) micellar eluent for determination of the total PET radioligand concentration. The simultaneous analysis of protein binding and radiometabolism of [(11)C]PBR28 was completed within 11 min without any pretreatment of plasma and employing a single analytical system. This system allowed highly sensitive analysis of total [(11)C]PBR28 with a limit of detection (LOD) of 1.6 becquerel (Bq). The LOD for the determination of unbound [(11)C]PBR28 was 21 Bq. Finally, simultaneous measurements of protein binding and radiometabolism of [(11)C]PBR28 in human plasma were achieved for up to 50 min after radioligand administration.

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Sample preparation techniques for protein binding measurement in radiopharmaceutical approaches: A short review

Moein

Halldin

2020

Talanta

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A simplified radiometabolite analysis procedure for PET radioligands using a solid phase extraction with micellar medium

Cited by 4 publications

References 26 publications

Dealing with PET radiometabolites

Dealing with PET radiometabolites

Simultaneous Determination of Protein-Free and Total Positron Emission Tomography Radioligand Concentrations in Plasma Using High-Performance Frontal Analysis Followed by Mixed Micellar Liquid Chromatography: Application to [¹¹C]PBR28 in Human Plasma

Sample preparation techniques for protein binding measurement in radiopharmaceutical approaches: A short review

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A simplified radiometabolite analysis procedure for PET radioligands using a solid phase extraction with micellar medium

Cited by 4 publications

References 26 publications

Dealing with PET radiometabolites

Dealing with PET radiometabolites

Simultaneous Determination of Protein-Free and Total Positron Emission Tomography Radioligand Concentrations in Plasma Using High-Performance Frontal Analysis Followed by Mixed Micellar Liquid Chromatography: Application to [11C]PBR28 in Human Plasma

Sample preparation techniques for protein binding measurement in radiopharmaceutical approaches: A short review

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Simultaneous Determination of Protein-Free and Total Positron Emission Tomography Radioligand Concentrations in Plasma Using High-Performance Frontal Analysis Followed by Mixed Micellar Liquid Chromatography: Application to [¹¹C]PBR28 in Human Plasma