Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation

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dc.contributor.authorCallaghan, PDen_AU
dc.contributor.authorWimberley, CAen_AU
dc.contributor.authorRahardjo, GLen_AU
dc.contributor.authorBerghofer, PJen_AU
dc.contributor.authorPham, TQen_AU
dc.contributor.authorJackson, TWen_AU
dc.contributor.authorZahra, Den_AU
dc.contributor.authorBourdier, Ten_AU
dc.contributor.authorWyatt, Nen_AU
dc.contributor.authorGreguric, Ien_AU
dc.contributor.authorHowell, NRen_AU
dc.contributor.authorSiegele, Ren_AU
dc.contributor.authorPastuovic, Zen_AU
dc.contributor.authorMattner, Fen_AU
dc.contributor.authorLoc'h, Cen_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorKatsifis, Aen_AU
dc.date.accessioned2017-05-14T23:57:21Zen_AU
dc.date.available2017-05-14T23:57:21Zen_AU
dc.date.issued2015-01en_AU
dc.date.statistics2015-05-15en_AU
dc.description.abstractThe in vivo binding parameters of the novel imidazopyridine TSPO ligand [18F]PBR102 were assessed and compared with those of [18F]PBR111 in a rodent model of neuroinflammation. The validity of the key assumptions of the simplified reference tissue model (SRTM) for estimation of binding potential (BP) was determined, with validation against a two-tissue compartment model (2TC). Methods Acute neuroinflammation was assessed 7 days after unilateral stereotaxic administration of (R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA) in anaesthetized adult Wistar rats. Anaesthetized rats were implanted with a femoral arterial cannula then injected with a low mass of [18F]PBR102 or [18F]PBR111 and dynamic images were acquired over 60 min using an INVEON PET/CT camera. Another population of rats underwent the same PET protocol after pretreatment with a presaturating mass of the same unlabelled tracer (1 mg/kg) to assess the validity of the reference region for SRTM analysis. Arterial blood was sampled during imaging, allowing pharmacokinetic determination of radiotracer concentrations. Plasma activity concentration–time curves were corrected for unchanged tracer based on metabolic characterization experiments in a separate cohort of Wistar rats. The stability of neuroinflammation in both imaging cohorts was assessed by [125I] CLINDE TSPO quantitative autoradiography, OX42/GFAP immunohistochemistry, Fluoro-Jade C histology, and elemental mapping using microparticle-induced x-ray emission spectroscopy. The BP of each ligand were assessed in the two cohorts of lesioned animals using both SRTM and a 2TC with arterial parent compound concentration, coupled with the results from the presaturation cohort for comparison and validation of the SRTM. Results The BPs of [18F]PBR102 [18F]PBR111 were equivalent, with improved signal-to-noise ratio and sensitivity compared with [11C]PK11195. The presaturation study showed differences in the volume of distribution between the ipsilateral striatum and the striatum contralateral to the injury (0.7) indicating that an assumption of the SRTM was not met. The modelling indicated that the BPs were consistent for both ligands. Between the SRTM and 2TC model, the BPs were highly correlated, but there was a bias in BP. Conclusion [18F]PBR102 and [18F]PBR111 have equivalent binding properties in vivo, displaying significantly greater BPs with lower signal-to-noise ratio than [11C]PK11195. While an assumption of the SRTM was not met, this modelling approach was validated against 2TC modelling for both ligands, facilitating future use in longitudinal PET imaging of neuroinflammation.© 2014, Springer Natureen_AU
dc.identifier.citationCallaghan, P. D., Wimberley, C. A., Rahardjo, G. L., Berghofer, P. J., Pham, T. Q., Jackson, T., Zahra, D., Bourdier, T., Wyatt, N., Greguric, I., Howell, N. R., Siegele, R., Pastuovic, Z., Mattner, F., Loc’h, C., Grégoire, M. C., & Katsifis, A. (2015). Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation. European Journal of Nuclear Medicine and Molecular Imaging, 42(1), 138-151. doi:10.1007/s00259-014-2895-3en_AU
dc.identifier.govdoc8221en_AU
dc.identifier.issn1619-7070en_AU
dc.identifier.issue1en_AU
dc.identifier.journaltitleEuropean Journal of Nuclear Medicine and Molecular Imagingen_AU
dc.identifier.pagination138-151en_AU
dc.identifier.urihttp://dx.doi.org/10.1007/s00259-014-2895-3en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/8697en_AU
dc.identifier.volume42en_AU
dc.language.isoenen_AU
dc.publisherSpringer Linken_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectInflammationen_AU
dc.subjectNeurologyen_AU
dc.subjectPIXE analysisen_AU
dc.subjectRatsen_AU
dc.subjectTracer techniquesen_AU
dc.titleComparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammationen_AU
dc.typeJournal Articleen_AU
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