Pharmacokinetic analysis of [11C]PBR28 in the rat model of herpes encephalitis: comparison with (R)-[11C]PK11195 for pre-clinical imaging

Paula Kopschina Feltes, Andrea Parente, David Vállez Garcia, Jurgen Sijbesma, Cristina Moriguchi Jeckel, Rudi Dierckx, Erik de Vries, Janine Doorduin

Research output: Contribution to conferenceAbstractAcademic

Abstract

Aim: [11C]PBR28 is a second generation translocator protein (TSPO) ligand with supposedly better imaging characteristics than the most commonly used tracer [11C]PK11195. Surprisingly, only limited studies have evaluated the pharmacokinetic and binding profile of [11C]PBR28 in neuroinflammatory models in rodents. For this reason, [11C]PBR28 was evaluated and compared to [11C]PK11195 for the detection and quantification of neuroinflammation for pre-clinical research.
Materials and methods: Herpes simplex encephalitis (HSE) was induced in male Wistar rats by intranasal inoculation of the herpes simplex type-1 virus, resulting in neuroinflammation. At 6-7 days post inoculation, 60-min dynamic [11C]PBR28 or [11C]PK11195 PET scans were performed. During the scans arterial blood samples were taken to generate blood and metabolite-corrected plasma input curves for pharmacokinetic modeling. Differences between control and HSE rats were assessed by voxel-based analysis, using standardized uptake values, and volume-of-interest analysis, using the reversible two-tissue compartment model to determine the binding potential (BPND).
Results: Voxel-based analysis showed that [11C]PBR28 was able to detect over-expression of TSPO in brain areas that are known to be affected in the HSE rat model. [11C]PBR28 had a faster metabolism than [11C]PK11195, with 50% of metabolites in plasma present at 5 min and 21 min, respectively. [11C]PBR28 demonstrated a higher sensitivity than [11C]PK11195 in the detection of neuroinflammation. The BPND of [11C]PBR28 was significantly higher (p<0.05) in the medulla (150%), pons (121%), midbrain (94%), thalamus (76%), hippocampus (65%), hypothalamus (44%) and cerebellum (37%) of HSE rats when compared to control rats, while a higher BPND of [11C]PK11195 was only found in the medulla (59%). Comparison of BPND between control groups showed no statistical difference, suggesting that non-specific binding of both tracers is similar.
Conclusion: [11C]PBR28 performed better than [11C]PK11195 in the detection of TSPO over-expression in the HSE rat model, as the BPND was found to be increased in more brain regions. The results of this study suggest that [11C]PBR28 is a better tool for pre-clinical research of neuroinflammation.
Original languageEnglish
PagesS117
DOIs
Publication statusPublished - Oct-2015
Event28th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) - Hamburg, Hamburg, Germany
Duration: 10-Oct-201514-Oct-2015

Conference

Conference28th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM)
CountryGermany
CityHamburg
Period10/10/201514/10/2015

Keywords

  • PET

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