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Jørgen Frøkiær

In Vivo Imaging of Human 11C-Metformin in Peripheral Organs: Dosimetry, Biodistribution and Kinetic Analyses

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In Vivo Imaging of Human 11C-Metformin in Peripheral Organs: Dosimetry, Biodistribution and Kinetic Analyses. / Gormsen, Lars Christian; Sundelin, Elias Immanuel; Jensen, Jonas Brorson; Vendelbo, Mikkel Holm; Jakobsen, Steen; Munk, Ole Lajord; Christensen, Mette Marie Hougaard; Brøsen, Kim; Frøkiær, Jørgen; Jessen, Niels.

In: The Journal of Nuclear Medicine, 28.07.2016.

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@article{a1580650f7e84601b9d71127ab87d65c,
title = "In Vivo Imaging of Human 11C-Metformin in Peripheral Organs: Dosimetry, Biodistribution and Kinetic Analyses",
abstract = "Metformin is the most widely prescribed oral anti-glycemic drug with few adverse effects. However, surprisingly little is known about its human biodistribution and target tissue metabolism. In animal experiments we have shown that metformin can be labelled by (11)C and that (11)C-metformin Positron emission tomography (PET) can be used to measure renal function. Here, we extend these pre-clinical findings by a first-in-human (11)C-metformin PET dosimetry, biodistribution and tissue kinetics study.METHODS: Nine subjects (three women, six men) participated in two studies: In the first study, human radiation dosimetry and biodistribution of (11)C-metformin were estimated in 4 subjects (two women and two men) by whole-body PET. In the second study, (11)C-metformin tissue kinetics were measured in response to both intravenous and oral radiotracer administration. A dynamic PET scan with a field-of-view covering target tissues of metformin (liver, kidneys, intestines and skeletal muscle) was performed for 90 (intravenous) and 120 (oral) minutes.RESULTS: Radiation dosimetry was acceptable with effective doses 9.5 (intravenous) and 18.1 μSv/MBq (oral) administrations. Whole body PET revealed, that (11)C-metformin was primarily taken up by the kidneys, urinary bladder and liver but also to a lesser extent in salivary glands, skeletal muscle and intestines. Reversible 2-tissue compartment kinetics was observed in the liver and volume of distribution (Vd) was calculated to be 2.45 ml/ml (arterial input) or 2.66 ml/ml (portal and arterial input). In the kidneys, compartmental models did not adequately fit the experimental data and Vd was therefore estimated by a linear approach to be 6.83 ml/ml. Skeletal muscle and intestinal tissue kinetics were best described by 2-tissue compartment kinetics and showed only discrete tracer uptake. Liver (11)C-metformin uptake was pronounced after oral administration of the tracer with tissue-to-blood ratio double what was observed after intravenous administration. Only slow accumulation of (11)C-metformin was observed in muscle. There was no elimination of (11)C-metformin through the bile both during the intravenous and the oral part of the study.CONCLUSION: (11)C-metformin is suitable for imaging metformin uptake in target tissues and may prove a valuable tool to assess the impact of metformin treatment in patients with varying metformin transport capacity.",
author = "Gormsen, {Lars Christian} and Sundelin, {Elias Immanuel} and Jensen, {Jonas Brorson} and Vendelbo, {Mikkel Holm} and Steen Jakobsen and Munk, {Ole Lajord} and Christensen, {Mette Marie Hougaard} and Kim Br{\o}sen and J{\o}rgen Fr{\o}ki{\ae}r and Niels Jessen",
note = "Copyright {\textcopyright} 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
year = "2016",
month = jul,
day = "28",
doi = "10.2967/jnumed.116.177774",
language = "English",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "SOC NUCLEAR MEDICINE INC",

}

RIS

TY - JOUR

T1 - In Vivo Imaging of Human 11C-Metformin in Peripheral Organs: Dosimetry, Biodistribution and Kinetic Analyses

AU - Gormsen, Lars Christian

AU - Sundelin, Elias Immanuel

AU - Jensen, Jonas Brorson

AU - Vendelbo, Mikkel Holm

AU - Jakobsen, Steen

AU - Munk, Ole Lajord

AU - Christensen, Mette Marie Hougaard

AU - Brøsen, Kim

AU - Frøkiær, Jørgen

AU - Jessen, Niels

N1 - Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2016/7/28

Y1 - 2016/7/28

N2 - Metformin is the most widely prescribed oral anti-glycemic drug with few adverse effects. However, surprisingly little is known about its human biodistribution and target tissue metabolism. In animal experiments we have shown that metformin can be labelled by (11)C and that (11)C-metformin Positron emission tomography (PET) can be used to measure renal function. Here, we extend these pre-clinical findings by a first-in-human (11)C-metformin PET dosimetry, biodistribution and tissue kinetics study.METHODS: Nine subjects (three women, six men) participated in two studies: In the first study, human radiation dosimetry and biodistribution of (11)C-metformin were estimated in 4 subjects (two women and two men) by whole-body PET. In the second study, (11)C-metformin tissue kinetics were measured in response to both intravenous and oral radiotracer administration. A dynamic PET scan with a field-of-view covering target tissues of metformin (liver, kidneys, intestines and skeletal muscle) was performed for 90 (intravenous) and 120 (oral) minutes.RESULTS: Radiation dosimetry was acceptable with effective doses 9.5 (intravenous) and 18.1 μSv/MBq (oral) administrations. Whole body PET revealed, that (11)C-metformin was primarily taken up by the kidneys, urinary bladder and liver but also to a lesser extent in salivary glands, skeletal muscle and intestines. Reversible 2-tissue compartment kinetics was observed in the liver and volume of distribution (Vd) was calculated to be 2.45 ml/ml (arterial input) or 2.66 ml/ml (portal and arterial input). In the kidneys, compartmental models did not adequately fit the experimental data and Vd was therefore estimated by a linear approach to be 6.83 ml/ml. Skeletal muscle and intestinal tissue kinetics were best described by 2-tissue compartment kinetics and showed only discrete tracer uptake. Liver (11)C-metformin uptake was pronounced after oral administration of the tracer with tissue-to-blood ratio double what was observed after intravenous administration. Only slow accumulation of (11)C-metformin was observed in muscle. There was no elimination of (11)C-metformin through the bile both during the intravenous and the oral part of the study.CONCLUSION: (11)C-metformin is suitable for imaging metformin uptake in target tissues and may prove a valuable tool to assess the impact of metformin treatment in patients with varying metformin transport capacity.

AB - Metformin is the most widely prescribed oral anti-glycemic drug with few adverse effects. However, surprisingly little is known about its human biodistribution and target tissue metabolism. In animal experiments we have shown that metformin can be labelled by (11)C and that (11)C-metformin Positron emission tomography (PET) can be used to measure renal function. Here, we extend these pre-clinical findings by a first-in-human (11)C-metformin PET dosimetry, biodistribution and tissue kinetics study.METHODS: Nine subjects (three women, six men) participated in two studies: In the first study, human radiation dosimetry and biodistribution of (11)C-metformin were estimated in 4 subjects (two women and two men) by whole-body PET. In the second study, (11)C-metformin tissue kinetics were measured in response to both intravenous and oral radiotracer administration. A dynamic PET scan with a field-of-view covering target tissues of metformin (liver, kidneys, intestines and skeletal muscle) was performed for 90 (intravenous) and 120 (oral) minutes.RESULTS: Radiation dosimetry was acceptable with effective doses 9.5 (intravenous) and 18.1 μSv/MBq (oral) administrations. Whole body PET revealed, that (11)C-metformin was primarily taken up by the kidneys, urinary bladder and liver but also to a lesser extent in salivary glands, skeletal muscle and intestines. Reversible 2-tissue compartment kinetics was observed in the liver and volume of distribution (Vd) was calculated to be 2.45 ml/ml (arterial input) or 2.66 ml/ml (portal and arterial input). In the kidneys, compartmental models did not adequately fit the experimental data and Vd was therefore estimated by a linear approach to be 6.83 ml/ml. Skeletal muscle and intestinal tissue kinetics were best described by 2-tissue compartment kinetics and showed only discrete tracer uptake. Liver (11)C-metformin uptake was pronounced after oral administration of the tracer with tissue-to-blood ratio double what was observed after intravenous administration. Only slow accumulation of (11)C-metformin was observed in muscle. There was no elimination of (11)C-metformin through the bile both during the intravenous and the oral part of the study.CONCLUSION: (11)C-metformin is suitable for imaging metformin uptake in target tissues and may prove a valuable tool to assess the impact of metformin treatment in patients with varying metformin transport capacity.

U2 - 10.2967/jnumed.116.177774

DO - 10.2967/jnumed.116.177774

M3 - Journal article

C2 - 27469359

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

ER -