Background and Aims: Kupffer cells are responsible for maintaining liver homeostasis and have a vital role in chronic hepatotoxicity and various liver diseases. Positron Imaging Tomography (PET) is a non-invasive imaging technique that allows quantification and visualization of biochemical processes by monitoring the distribution of molecules labelled with positron imaging isotopes. We aimed to develop a methodology for noninvasive PET imaging of Kupffer cell status in liver. Methods: Our strategy was to target CD206 receptor that selectively takes up mannosylated albumin. Thus mannosylated albumin (mHSA) was synthesized and coupled to radionuclide-18F. Thereafter the pharmacological properties of this radiotracer were explored in a range of pre-clinical models including cells and wistar-rats. Whole-body PET images were acquired 30/60 minutes after injection of 5-15 MBq of radiotracer-[18F]B-mHSA. Results: Hepatic uptake at 30 and 60 min was high whereas accumulation in the kidney was even higher, due to metabolism in liver and renal clearance. Blocking studies with a 20 fold excess of unlabeled tracer revealed saturable tracer uptake. In immune-related organs such as the bone-marrow, spleen, and liver radio-tracer uptake was highest at 30 minutes post injection and decreased thereafter. Ex-vivo biodistribution indicated lowest tracer uptake in non-target organs. Tracer uptake reaches a plateau in 45 min for RAW cells and in 60 min for murine Kupffer cells. Conclusions: [18F]B-mHSA is readily labelled, is stable in plasma and displays binding affinity for the CD206 receptors. This method allows quantitative and non-invasive imaging of liver function by using expression of the Kupffer cell specific CD206 receptor with special interest in liver toxicity and the early events leading to liver fibrosis.