A PET Tracer for Renal Organic Cation Transporters, ¹¹C-Metformin: Radiosynthesis and Preclinical Proof-of-Concept Studies

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Steen JakobsenJørgen Frøkiær

Abstract

Organic cation transporters (OCTs) in the kidney proximal tubule (PT) participate in renal excretion of drugs and endogenous compounds. PT function is commonly impaired in kidney diseases, and consequently quantitative measurement of OCT function may provide an important estimate of kidney function. Metformin is a widely used drug and targets OCT type 2 located in the PT. Thus, we hypothesized that (11)C-labeled metformin would be a suitable PET tracer for quantification of renal function. (11)C-metformin was prepared by (11)C-methylation of 1-methylbiguanide. In vitro cell uptake of (11)C-metformin was studied in LLC-PK1 cells in the presence of increasing doses of unlabeled metformin. In vivo small-animal PET studies in Sprague-Dawley rats were performed at baseline and after treatment with OCT inhibitors to evaluate renal uptake of (11)C-metformin. Kidney and liver pharmacokinetics of (11)C-metformin was investigated in vivo by dynamic (11)C-metformin PET/CT in 6 anesthetized pigs, and renal clearance of (11)C-metformin was compared with renal clearance of (51)Cr-ethylenediaminetetraacetic acid (EDTA). Formation of (11)C metabolites was investigated by analysis of blood and urine samples. The radiochemical yield of (11)C-met...Continue Reading

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Citations

Apr 6, 2017·Clinical Pharmacology and Therapeutics·Eio SundelinN Jessen
May 13, 2018·Diabetes, Obesity & Metabolism·Peter BreiningNiels Jessen
Apr 3, 2020·Breast Cancer Research and Treatment·Elias Immanuel Ordell SundelinNiels Jessen
Apr 12, 2019·British Journal of Clinical Pharmacology·Elias Immanuel Ordell SundelinNiels Jessen
Jun 12, 2019·Contrast Media & Molecular Imaging·Maria Dahl OvergaardMichael Pedersen
Sep 9, 2020·Endocrine Reviews·Traci E LaMoia, Gerald I Shulman
Jul 30, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Lars C GormsenNiels Jessen
Jun 2, 2020·The Journal of Clinical Endocrinology and Metabolism·Elias SundelinNiels Jessen

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