Publication

Non-invasive imaging of Kupffer cell status using radiolabelled mannosylated albumin

Mahajan, V., Hartimath, S., Comley, R., Poelstra, K., Reker-Smit, C., Kamps, J., Sijbesma, J., Stephan-Gueldner, M., Dierckx, R. & de Vries, E., 1-May-2014, In : Journal of Nuclear Medicine. 55, Supplement 1, 1 p.

Research output: Contribution to journalMeeting AbstractAcademic

Objectives Kupffer cells (KCs) play a key role in maintaining liver homeostasis, hepatotoxicity and in liver pathology, but their functional status cannot be directly assessed in vivo (1-5). We report a PET tracer for noninvasive translational imaging of KCs. Methods A mannosylated human serum albumin (18mHSA), that binds to CD206 receptor [on KCs and M2-macrophages(6-7)], was synthesized, labelled by conjugation with N-succinimidyl 4-[18F]fluorobenzoate ([18F]FB). Pharmacological properties of [18F]FB18mHSA were investigated by ex vivo biodistribution and blocking studies at 30, 60 min (n=5). A 60min dynamic PET imaging studies with arterial blood sampling were performed in rats after injection of ~15 MBq of [18F]FB18mHSA (n=5). Results [18F]FB18mHSA was stable rat plasma in vitro, but showed significant metabolism in vivo (16% parent at 60 min). Radioactivity in blood decreased from the first time-point (10 sec) onward. Ex vivo biodistribution showed hepatic uptake was high (SUV 11.4±2.4 (mean±SD) at 30 min; SUV 8.9±3.3 at 60 min), as was accumulation in the kidney (SUV 24±7), due to metabolism in liver and rapid clearance of radioactivity from the blood pool via renal-urinary route. Blocking with a 20 fold excess of the unlabelled 18-mHSA, significantly decreased the uptake in liver (SUV 0.8±1.2 at 30 min, p<0.0005; SUV 4.5±0.7 at 60 min; p<0.05) and organs with immune function like bone-marrow (84%, p<0.0005) and spleen (90%, p<0.0005). PET data was analysed by Logan and Patlak graphical analysis using the metabolite-corrected plasma curve. Data was well described by Logan model, but not by Patlak model, indicating reversible binding kinetics. Conclusions [18F]FB18mHSA allows quantitative noninvasive PET imaging of the KCs and this novel method might be useful to investigate liver toxicity and fibrosis.
Original languageEnglish
Number of pages1
JournalJournal of Nuclear Medicine
Volume55
Issue numberSupplement 1
Publication statusPublished - 1-May-2014

ID: 16299913