Jørgen Frøkiær

Metformin is distributed to tumor tissue in breast cancer patients in vivo: A 11C-metformin PET/CT study

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Metformin is distributed to tumor tissue in breast cancer patients in vivo : A 11C-metformin PET/CT study. / Sundelin, Elias Immanuel Ordell; al-Suliman, Nidal; Vahl, Pernille; Vendelbo, Mikkel; Munk, Ole Lajord; Jakobsen, Steen; Pedersen, Steen Bønløkke; Frøkiær, Jørgen; Gormsen, Lars C.; Jessen, Niels.

In: Breast Cancer Research and Treatment, Vol. 181, No. 1, 05.2020, p. 107-113.

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@article{a2f1283d1e314dbba5ad7f6959cb484a,
title = "Metformin is distributed to tumor tissue in breast cancer patients in vivo: A 11C-metformin PET/CT study",
abstract = "Purpose: Epidemiological studies and randomized clinical trials suggest that the antidiabetic drug, metformin, may have anti-neoplastic effects. The mechanism that mediates these beneficial effects has been suggested to involve direct action on cancer cells, but this will require distribution of metformin in tumor tissue. The present study was designed to investigate metformin distribution in vivo in breast and liver tissue in breast cancer patients. Methods: Seven patients recently diagnosed with ductal carcinoma were recruited. Using PET/CT, tissue distribution of metformin was determined in vivo for 90 min after injection of a carbon-11-labeled metformin tracer. After surgery, tumor tissue was investigated for gene expression levels of metformin transporter proteins. Results: Tumor tissue displayed a distinct uptake of metformin compared to normal breast tissue AUC0-90 min (75.4 ± 5.5 vs 42.3 ± 6.3) g/ml*min (p = 0.01). Maximal concentration in tumor was at 1 min where it reached approximately 30% of the activity in the liver. The metformin transporter protein with the highest gene expression in tumor tissue was multidrug and toxin extrusion 1 (MATE 1) followed by plasma membrane monoamine transporter (PMAT). Conclusion: This study confirms that metformin is transported into tumor tissue in women with breast cancer. This finding support that metformin may have direct anti-neoplastic effects on tumor cells in breast cancer patients. However, distribution of metformin in tumor tissue is markedly lower than in liver, an established metformin target tissue.",
keywords = "Antidiabetic treatment, Ductal carcinoma, Oncology, Organic cation transporters",
author = "Sundelin, {Elias Immanuel Ordell} and Nidal al-Suliman and Pernille Vahl and Mikkel Vendelbo and Munk, {Ole Lajord} and Steen Jakobsen and Pedersen, {Steen B{\o}nl{\o}kke} and J{\o}rgen Fr{\o}ki{\ae}r and Gormsen, {Lars C.} and Niels Jessen",
year = "2020",
month = may,
doi = "10.1007/s10549-020-05621-6",
language = "English",
volume = "181",
pages = "107--113",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York LLC",
number = "1",

}

RIS

TY - JOUR

T1 - Metformin is distributed to tumor tissue in breast cancer patients in vivo

T2 - A 11C-metformin PET/CT study

AU - Sundelin, Elias Immanuel Ordell

AU - al-Suliman, Nidal

AU - Vahl, Pernille

AU - Vendelbo, Mikkel

AU - Munk, Ole Lajord

AU - Jakobsen, Steen

AU - Pedersen, Steen Bønløkke

AU - Frøkiær, Jørgen

AU - Gormsen, Lars C.

AU - Jessen, Niels

PY - 2020/5

Y1 - 2020/5

N2 - Purpose: Epidemiological studies and randomized clinical trials suggest that the antidiabetic drug, metformin, may have anti-neoplastic effects. The mechanism that mediates these beneficial effects has been suggested to involve direct action on cancer cells, but this will require distribution of metformin in tumor tissue. The present study was designed to investigate metformin distribution in vivo in breast and liver tissue in breast cancer patients. Methods: Seven patients recently diagnosed with ductal carcinoma were recruited. Using PET/CT, tissue distribution of metformin was determined in vivo for 90 min after injection of a carbon-11-labeled metformin tracer. After surgery, tumor tissue was investigated for gene expression levels of metformin transporter proteins. Results: Tumor tissue displayed a distinct uptake of metformin compared to normal breast tissue AUC0-90 min (75.4 ± 5.5 vs 42.3 ± 6.3) g/ml*min (p = 0.01). Maximal concentration in tumor was at 1 min where it reached approximately 30% of the activity in the liver. The metformin transporter protein with the highest gene expression in tumor tissue was multidrug and toxin extrusion 1 (MATE 1) followed by plasma membrane monoamine transporter (PMAT). Conclusion: This study confirms that metformin is transported into tumor tissue in women with breast cancer. This finding support that metformin may have direct anti-neoplastic effects on tumor cells in breast cancer patients. However, distribution of metformin in tumor tissue is markedly lower than in liver, an established metformin target tissue.

AB - Purpose: Epidemiological studies and randomized clinical trials suggest that the antidiabetic drug, metformin, may have anti-neoplastic effects. The mechanism that mediates these beneficial effects has been suggested to involve direct action on cancer cells, but this will require distribution of metformin in tumor tissue. The present study was designed to investigate metformin distribution in vivo in breast and liver tissue in breast cancer patients. Methods: Seven patients recently diagnosed with ductal carcinoma were recruited. Using PET/CT, tissue distribution of metformin was determined in vivo for 90 min after injection of a carbon-11-labeled metformin tracer. After surgery, tumor tissue was investigated for gene expression levels of metformin transporter proteins. Results: Tumor tissue displayed a distinct uptake of metformin compared to normal breast tissue AUC0-90 min (75.4 ± 5.5 vs 42.3 ± 6.3) g/ml*min (p = 0.01). Maximal concentration in tumor was at 1 min where it reached approximately 30% of the activity in the liver. The metformin transporter protein with the highest gene expression in tumor tissue was multidrug and toxin extrusion 1 (MATE 1) followed by plasma membrane monoamine transporter (PMAT). Conclusion: This study confirms that metformin is transported into tumor tissue in women with breast cancer. This finding support that metformin may have direct anti-neoplastic effects on tumor cells in breast cancer patients. However, distribution of metformin in tumor tissue is markedly lower than in liver, an established metformin target tissue.

KW - Antidiabetic treatment

KW - Ductal carcinoma

KW - Oncology

KW - Organic cation transporters

UR - http://www.scopus.com/inward/record.url?scp=85082832964&partnerID=8YFLogxK

U2 - 10.1007/s10549-020-05621-6

DO - 10.1007/s10549-020-05621-6

M3 - Journal article

C2 - 32240455

AN - SCOPUS:85082832964

VL - 181

SP - 107

EP - 113

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 1

ER -