Non-invasive imaging of kupffer cell status using radiolabelled mannosylated albuminMahajan, V., Hartimath, S., Comley, R., Stefan-Gueldner, M., Roth, A., Poelstra, K., Reker-Smit, C., Kamps, J., Dierckx, R. & de Vries, E., 1-Apr-2014, In : Journal of Hepatology. 60, 1, Suppl., p. S180-S181 2 p.
Research output: Contribution to journal › Meeting Abstract › Academic
- Pharmacokinetics, Toxicology and Targeting
- Science and Engineering Faculty Board
- Center for Medical Imaging (CMI)
- Molecular Neuroscience and Ageing Research (MOLAR)
- Nanobiotechnology and Advanced Therapeutic Materials (NANOBIOMAT)
- Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
- Vascular Ageing Programme (VAP)
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.
|Number of pages||2|
|Journal||Journal of Hepatology|
|Issue number||1, Suppl.|
|Publication status||Published - 1-Apr-2014|
- albumin, tracer, receptor, fluorine 18, radioisotope, isotope, liver, Kupffer cell, imaging, liver toxicity, positron, injection, Wistar rat, model, binding affinity, plasma, target organ, liver function, liver fibrosis, ex vivo study, whole body PET, methodology, bone marrow, monitoring, kidney clearance, biochemistry, spleen, metabolism, kidney, tomography, liver disease, homeostasis