Metabolite analysis in positron emission tomography studies: examples from food sciences

Pawelke, B.

doi:10.1007/s00726-005-0202-0

Cited by 20 publications

(17 citation statements)

References 64 publications

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“…The PET radionuclides that are most widely used usually include 11 C (t 1/2 = 20.39 min), 13 N (t 1/2 = 9.97 min), and 15 O (t 1/2 = 2 min). Although carbon, nitrogen and oxygen are the main constituents in most important molecules with biological activity and their isotopes have very small kinetic isotope effects, it is difficult to obtain total recovery of the radioactivity from the whole organism due to their short radioactive half-lives [15]. Therefore, positron emitting fluorine-18 ( 18 F)-labelled compounds were synthesized, which allowed the measurement the radioactivity distribution time profile and the radioactivity concentration in biological samples without destruction of the tissues and unaffected by the chemical composition of the studied samples.…”

Section: Introductionmentioning

confidence: 99%

Biodistribution and Elimination Study of Fluorine-18 Labeled Nε-Carboxymethyl-Lysine following Intragastric and Intravenous Administration

Wang

Wang³

et al. 2013

PLoS ONE

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BackgroundNε-carboxymethyl-lysine (CML) is a major advanced glycation end-product (AGEs) widely found in foods. The aim of our study was to evaluate how exogenous CML-peptide is dynamically absorbed from the gastrointestinal tract and eliminated by renal tubular secretion using microPET imaging.MethodsThe present study consisted of three investigations. In study I, we synthesized the imaging tracer 18F-CML by reacting N-succinimidyl 4-18F-fluorobenzoate (18F-SFB) with CML. In study II, the biological activity of 18F-CML was evaluated in RAW264.7 cells and HepG2 cells. In study III, the biodistribution and elimination of AGEs in ICR mice were studied in vivo following tail vein injection and intragastric administration of 18F-CML.ResultThe formation of 18F-CML was confirmed by comparing its retention time with the corresponding reference compound 19F-CML. The radiochemical purity (RCP) of 18F-CML was >95%, and it showed a stable character in vitro and in vivo. Uptake of 18F-CML by RAW264.7 cells and HepG2 cells could be inhibited by unmodified CML. 18F-CML was quickly distributed via the blood, and it was rapidly excreted through the kidneys 20 min after tail vein injection. However, 18F-CML was only slightly absorbed following intragastric administration. After administration of 18F-CML via a stomach tube, the radioactivity was completely localized in the stomach for the first 15 min. At 150 min post intragastric administration, intense accumulation of radioactivity in the intestines was still observed.ConclusionsPET technology is a powerful tool for the in vivo analysis of the gastrointestinal absorption of orally administered drugs. 18F-CML is hardly absorbed by the gastrointestinal tract. It is rapidly distributed and eliminated from blood following intravenous administration. Thus, it may not be harmful to healthy bodies. Our study showed the feasibility of noninvasively imaging 18F-labeled AGEs and was the first to describe CML-peptide gastrointestinal absorption by means of PET.

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Section: Introductionmentioning

confidence: 99%

Biodistribution and Elimination Study of Fluorine-18 Labeled Nε-Carboxymethyl-Lysine following Intragastric and Intravenous Administration

Wang

Wang³

et al. 2013

PLoS ONE

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“…PET is currently the most useful imaging technique for noninvasive, regional measurement of drug pharmacokinetics in a variety of tissues 26 . The most significant benefit of the microPET scanners compared to other traditional functional imaging methods, such as autoradiography and direct tissue counting (biodistribution), is that the animal can be scanned in vivo .…”

Section: Functional Imagingmentioning

confidence: 99%

“…The most convenient radioisotopes are 18 F with a half‐life of 109.7 min and 11 C with a half‐life of 20.4 min. The short half‐life of PET radionuclides permits repetitive and longitudinal studies before and after experimental treatment 26 …”

Section: Functional Imagingmentioning

confidence: 99%

Anatomical and Functional Imaging of Tumors in Animal Models

Martiniova

Guion

Schimel

et al. 2006

Annals of the New York Academy of Sciences

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This review focuses on anatomical (computed tomography, magnetic resonance imaging) and functional (positron emission tomography) imaging methods for tumor localization and identification of experimentally induced tumors in animal models, especially pheochromocytoma. Although anatomical imaging can precisely locate primary and metastatic tumors, functional imaging has high specificity for some tumors, especially those of endocrine origin. This is due to the fact that endocrine tumor cells take up hormone precursors, express hormone receptors and transporters, and synthesize, store, and release hormones. These characteristic properties of endocrine tumors enable investigators to create highly specific radiopharmaceuticals, particularly for positron emission tomography. For example, localization of pheochromocytoma involves [18F]-6F-dopamine. It is a highly specific radiopharmaceutical since it uses the norepinephrine transporter system expressed in most pheochromocytoma cells. Here we review both anatomical and functional imaging methods that are used conjointly in order to localize and identify specific characteristics of tumors.

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“…The detector only detects the annihilation photons from the decaying positron-emitting isotope and cannot distinguish whether the radionuclide remains attached to the parent tracer or its metabolites (1). AIF can also be image derived obtained by measuring the activity in an arterial region in dynamic PET.…”

Section: Introductionmentioning

confidence: 99%

Plasma radio–metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography

Hicks

et al. 2020

Preprint

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Background In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma, however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers - [18F]FAZA and [18F]FEPPA , for imaging hypoxia and inflammation respectively. Results Radioactivity as low as 17Bq in 2µL of pig’s plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n=8) in the autoradiographic image. Significant inter-subject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [18F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5 min post injection while for [18F]FAZA, significant metabolites did not appear until 50 min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32-400% parameter error can result without radio-metabolites correction.Conclusion TLC coupled with autoradiography is a good alternative to high performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 mL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies.

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Metabolite analysis in positron emission tomography studies: examples from food sciences

Cited by 20 publications

References 64 publications

Biodistribution and Elimination Study of Fluorine-18 Labeled Nε-Carboxymethyl-Lysine following Intragastric and Intravenous Administration

Biodistribution and Elimination Study of Fluorine-18 Labeled Nε-Carboxymethyl-Lysine following Intragastric and Intravenous Administration

Anatomical and Functional Imaging of Tumors in Animal Models

Plasma radio–metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography

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