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

Lars C Gormsen, Elias Immanuel Sundelin, Jonas Brorson Jensen, Mikkel Holm Vendelbo, Steen Jakobsen, Ole Lajord Munk, Mette Marie Hougaard Christensen, Kim Brøsen, Jørgen Frøkiær, Niels Jessen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Metformin is the most widely prescribed oral antiglycemic 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 labeled by (11)C and that (11)C-metformin PET can be used to measure renal function. Here, we extend these preclinical findings by a first-in-human (11)C-metformin PET dosimetry, biodistribution, and tissue kinetics study.

METHODS: Nine subjects (3 women and 6 men) participated in 2 studies: in the first study, human radiation dosimetry and biodistribution of (11)C-metformin were estimated in 4 subjects (2 women and 2 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 obtained for 90 (intravenous) and 120 (oral) min.

RESULTS: Radiation dosimetry was acceptable, with effective doses of 9.5 μSv/MBq (intravenous administration) and 18.1 μSv/MBq (oral administration). 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 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 volume of distribution 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 during 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.

OriginalsprogEngelsk
TidsskriftThe Journal of Nuclear Medicine
Vol/bind57
Udgave nummer12
Sider (fra-til)1920-1926
ISSN0161-5505
DOI
StatusUdgivet - 2016

Fingeraftryk

Radiometry
Kidney
Skeletal Muscle
Liver
Intestines
Muscles
Pharmaceutical Preparations

Citer dette

Gormsen, L. C., Sundelin, E. I., Jensen, J. B., Vendelbo, M. H., Jakobsen, S., Munk, O. L., ... Jessen, N. (2016). In Vivo Imaging of Human 11C-Metformin in Peripheral Organs: Dosimetry, Biodistribution, and Kinetic Analyses. The Journal of Nuclear Medicine, 57(12), 1920-1926. https://doi.org/10.2967/jnumed.116.177774
Gormsen, Lars C ; Sundelin, Elias Immanuel ; Jensen, Jonas Brorson ; Vendelbo, Mikkel Holm ; Jakobsen, Steen ; Munk, Ole Lajord ; Hougaard Christensen, Mette Marie ; Brøsen, Kim ; Frøkiær, Jørgen ; Jessen, Niels. / In Vivo Imaging of Human 11C-Metformin in Peripheral Organs : Dosimetry, Biodistribution, and Kinetic Analyses. I: The Journal of Nuclear Medicine. 2016 ; Bind 57, Nr. 12. s. 1920-1926.
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In Vivo Imaging of Human 11C-Metformin in Peripheral Organs : Dosimetry, Biodistribution, and Kinetic Analyses. / Gormsen, Lars C; Sundelin, Elias Immanuel; Jensen, Jonas Brorson; Vendelbo, Mikkel Holm; Jakobsen, Steen; Munk, Ole Lajord; Hougaard Christensen, Mette Marie; Brøsen, Kim; Frøkiær, Jørgen; Jessen, Niels.

I: The Journal of Nuclear Medicine, Bind 57, Nr. 12, 2016, s. 1920-1926.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - In Vivo Imaging of Human 11C-Metformin in Peripheral Organs

T2 - Dosimetry, Biodistribution, and Kinetic Analyses

AU - Gormsen, Lars C

AU - Sundelin, Elias Immanuel

AU - Jensen, Jonas Brorson

AU - Vendelbo, Mikkel Holm

AU - Jakobsen, Steen

AU - Munk, Ole Lajord

AU - Hougaard Christensen, Mette Marie

AU - Brøsen, Kim

AU - Frøkiær, Jørgen

AU - Jessen, Niels

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

PY - 2016

Y1 - 2016

N2 - Metformin is the most widely prescribed oral antiglycemic 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 labeled by (11)C and that (11)C-metformin PET can be used to measure renal function. Here, we extend these preclinical findings by a first-in-human (11)C-metformin PET dosimetry, biodistribution, and tissue kinetics study.METHODS: Nine subjects (3 women and 6 men) participated in 2 studies: in the first study, human radiation dosimetry and biodistribution of (11)C-metformin were estimated in 4 subjects (2 women and 2 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 obtained for 90 (intravenous) and 120 (oral) min.RESULTS: Radiation dosimetry was acceptable, with effective doses of 9.5 μSv/MBq (intravenous administration) and 18.1 μSv/MBq (oral administration). 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 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 volume of distribution 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 during 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 antiglycemic 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 labeled by (11)C and that (11)C-metformin PET can be used to measure renal function. Here, we extend these preclinical findings by a first-in-human (11)C-metformin PET dosimetry, biodistribution, and tissue kinetics study.METHODS: Nine subjects (3 women and 6 men) participated in 2 studies: in the first study, human radiation dosimetry and biodistribution of (11)C-metformin were estimated in 4 subjects (2 women and 2 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 obtained for 90 (intravenous) and 120 (oral) min.RESULTS: Radiation dosimetry was acceptable, with effective doses of 9.5 μSv/MBq (intravenous administration) and 18.1 μSv/MBq (oral administration). 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 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 volume of distribution 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 during 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

VL - 57

SP - 1920

EP - 1926

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 12

ER -