Pharmacokinetic modelling of N-(4-[F-18]fluorobenzoyl)interleukin-2 binding to activated lymphocytes in an xenograft model of inflammation

Valentina Di Gialleonardo, Alberto Signore*, Antoon T. M. Willemsen, Jurgen W. A. Sijbesma, Rudi A. J. O. Dierckx, Erik F. J. de Vries

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

21 Citaten (Scopus)

Samenvatting

N-(4-[F-18]Fluorobenzoyl)interleukin-2 ([F-18]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 [F-18]FB-IL2 can be used to quantify activated human peripheral blood mononuclear cells (hPBMC) in rats by pharmacokinetic modelling.

Eleven Wistar rats were subcutaneously inoculated in the shoulder with different amounts of phytohaemagglutinin (PHA) activated hPBMC 15 min before i.v. injection of [F-18]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.

A 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 [F-18]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 mu l lesion (95 % confidence).

[F-18]FB-IL2 kinetics in this animal model of inflammation could be best described by a reversible two-tissue compartment model. The [F-18]FB-IL2 binding potential is a suitable measure for accurate quantification of lymphocytic infiltration in pathological conditions with PET.

Originele taal-2English
Pagina's (van-tot)1551-1560
Aantal pagina's10
TijdschriftEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume39
Nummer van het tijdschrift10
DOI's
StatusPublished - okt-2012

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