Abstract
Purpose N-(4-[18F]Fluorobenzoyl)interleukin-2 ([18F]FB-IL2) specifically binds to interleukin-2 receptors (IL-2R) and thus may be used to detect inflammation processes using positron emission tomography (PET). We now validated whether [18F]FB-IL2 can be used to quantify activated human peripheral blood mononuclear cells (hPBMC) in rats by pharmacokinetic modelling.MethodsEleven Wistar rats were subcutaneously inoculated in the shoulder with different amounts of phytohaemagglutinin (PHA) activated hPBMC 15 min before i.v. injection of [18F]FB-IL2. A 60-min dynamic PET scan was acquired and arterial blood sampling and metabolite analysis were performed. At the end of the scan, animals were terminated and the inflammatory lesion dissected. PET data were analysed using Logan and Patlak analysis as well as one-tissue and two-tissue compartment models. Model preferences according to the Akaike information criterion (AIC) and correlation between PET measurements and the number of CD25-positive cells were evaluated.ResultsA high correlation between ex vivo tracer uptake (standardized uptake value) in the xenograft and the number of inoculated CD25-positive cells was observed (R 2 = 0.90). Plasma time-activity curves showed a rapid washout of the radiopharmaceutical from blood, while the time-activity curves of the inflammatory lesions showed slower washout. Time-activity curves could be fitted well by the Logan analysis method, indicating that the binding between [18F]FB-IL2 and CD25 is reversible. AIC indicated that data could be modelled best by a two-tissue reversible compartment model. A high correlation was observed between the binding potential and the number of CD25-positive cells (R 2 = 0.876, p < 0.0001). Based on binding potential measured by PET, the limit of detection was about 160,000 CD25-positive cells per 200 μl lesion (95 % confidence).Conclusion[18F]FB-IL2 kinetics in this animal model of inflammation could be best described by a reversible two-tissue compartment model. The [18F]FB-IL2 binding potential is a suitable measure for accurate quantification of lymphocytic infiltration in pathological conditions with PET.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-012-2176-y) contains supplementary material, which is available to authorized users.
Highlights
High levels of interleukin-2 receptors (IL-2R) can be found mainly on the surface of activated T lymphocytes [1,2,3] after endogenous stimulation
Human blood was obtained from the local blood bank. human peripheral blood mononuclear cells (hPBMC) were isolated from human peripheral blood by density gradient medium centrifugation (Lymphoprep, Axis-Shield) using the rapid centrifugation procedure developed by Bøyum [23, 24]
The number of the inoculated hPBMC was corrected for the fraction of CD25-positive cells before correlation with the positron emission tomography (PET) results
Summary
High levels of interleukin-2 receptors (IL-2R) can be found mainly on the surface of activated T lymphocytes (both CD4+ and CD8+, mainly Th1 lymphocytes) [1,2,3] after endogenous stimulation. Eur J Nucl Med Mol Imaging (2012) 39:1551–1560 processes, such as tissue degeneration [4,5,6], autoimmune diseases [7, 8], viral, fungal and mycobacterial infections, graft rejection and in tumour infiltrates [9,10,11,12,13,14,15]. These disorders are characterized by the activation of the immune system and slow recruitment of immune cells (peripheral blood mononuclear cell, PBMC) in the lesion. Because IL-2R expression is low in resting immune cells, the receptor might be a suitable biomarker to study active inflammation in chronic inflammatory diseases
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