This study emphasizes the role of FAZA PET/CT imaging as a suitable assay with prognostic potential for detection of hypoxia in HNSCC.

Erlotinib (Tarceva) targets the epidermal growth factor receptor (EGFR), which is commonly overexpressed in human cancers, including lung cancer. We show that erlotinib can be labeled with [11 C] by reacting the normethyl precursor with [ 11

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 mSv/MBq (intravenous administration) and 18

Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates the application of novel imaging techniques to investigate pharmacogenetic properties in humans.

Metformin is the most commonly prescribed oral antidiabetic drug, with well-documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [11C]-labeled metformin ([11C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [11C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies.