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. 2020 May;181(1):107-113.
doi: 10.1007/s10549-020-05621-6. Epub 2020 Apr 2.

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

Elias Immanuel Ordell Sundelin  1 , Nidal Al-Suliman  2 , Pernille Vahl  3 , Mikkel Vendelbo  4 , Ole Lajord Munk  4 , Steen Jakobsen  4 , Steen Bønløkke Pedersen  5   6 , Jørgen Frøkiær  4 , Lars C Gormsen  4 , Niels Jessen  7   8   9   10   11
Affiliations

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

Elias Immanuel Ordell Sundelin et al. Breast Cancer Res Treat. 2020 May.

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.

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References

    1. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D (2010) Diabetes and cancer a: consensus report. CA: Cancer J Clinicians 60(4):207–221. https://doi.org/10.3322/caac.20078 - DOI
    1. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B (2005) Diabetes mellitus and breast cancer. Lancet Oncol 6(2):103–111. https://doi.org/10.1016/S1470-2045(05)01736-5 - DOI - PubMed
    1. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330(7503):1304–1305. https://doi.org/10.1136/bmj.38415.708634.F7 - DOI - PubMed - PMC
    1. Bowker SL, Majumdar SR, Veugelers P, Johnson JA (2006) Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29(2):254–258 - DOI
    1. Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, Jellema G, Deharo S, Hardie DG, Pusztai L, Moulder-Thompson S, Dewar JA, Thompson AM (2011) Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 128(3):783–794. https://doi.org/10.1007/s10549-011-1612-1 - DOI - PubMed

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