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  • Plaven-Sigray, PontusKarolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm Cty Council, Stockholm Hlth Care Serv, SE-17176 Stockholm, Sweden. (author)

Accuracy and reliability of [C-11]PBR28 specific binding estimated without the use of a reference region

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • ACADEMIC PRESS INC ELSEVIER SCIENCE,2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-440715
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-440715URI
  • https://doi.org/10.1016/j.neuroimage.2018.11.020DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:140408888URI

Supplementary language notes

  • Language:English
  • Summary in:English &language:-1_t

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • [C-11]PBR28 is a positron emission tomography radioligand used to examine the expression of the 18 kDa translocator protein (TSPO). TSPO is located in glial cells and can function as a marker for immune activation. Since TSPO is expressed throughout the brain, no true reference region exists. For this reason, an arterial input function is required for accurate quantification of [C-11]PBR28 binding and the most common outcome measure is the total distribution volume (V-T). Notably, V-T reflects both specific binding and non-displaceable binding. Therefore, estimates of specific binding, such as binding potential (e.g. BPND) and specific distribution volume (V-S) should theoretically be more sensitive to underlying differences in TSPO expression. It is unknown, however, if unbiased and accurate estimates of these outcome measures are obtainable for [C-11]PBR28. The Simultaneous Estimation (SIME) method uses time-activity-curves from multiple brain regions with the aim to obtain a brain-wide estimate of the non-displaceable distribution volume (V-ND), which can subsequently be used to improve the estimation of BPND and V-S. In this study we evaluated the accuracy of SIME-derived V-ND, and the reliability of resulting estimates of specific binding for [C-11]PBR28, using a combination of simulation experiments and in vivo studies in healthy humans. The simulation experiments, based on data from 54 unique [C-11]PBR28 examinations, showed that V-ND values estimated using SIME were both precise and accurate. Data from a pharmacological competition challenge (n = 5) showed that SIME provided V-ND values that were on average 19% lower than those obtained using the Lassen plot, but similar to values obtained using the Likelihood-Estimation of Occupancy technique. Test-retest data (n = 11) showed that SIME-derived V-S values exhibited good reliability and precision, while larger variability was observed in SIME-derived BPND values. The results support the use of SIME for quantifying specific binding of [C-11]PBR28, and suggest that V-S can be used in complement to the conventional outcome measure V-T. Additional studies in patient cohorts are warranted.

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  • Schain, MartinCopenhagen Univ Hosp, Neurobiol Res Unit, Copenhagen, Denmark. (author)
  • Zanderigo, FrancescaColumbia Univ, Dept Psychiat, New York, NY USA.;New York State Psychiat Inst & Hosp, Mol Imaging & Neuropathol Div, New York, NY 10032 USA. (author)
  • Farde, LarsKarolinska Institutet (author)
  • Halldin, ChristerKarolinska Institutet (author)
  • Forsberg, AntonKarolinska Institutet (author)
  • Varrone, AndreaKarolinska Institutet (author)
  • Jucaite, AurelijaKarolinska Institutet (author)
  • Cervenka, SimonKarolinska Institutet(Swepub:uu)simce160 (author)
  • Stenkrona, PerKarolinska Institutet (author)
  • Collste, KarinKarolinska Institutet (author)
  • Kander, Matsle (author)
  • Kosek, EvaKarolinska Institutet(Swepub:uu)evako353 (author)
  • Lampa, JonKarolinska Institutet (author)
  • Hoglund, Caroline Olgart (author)
  • Rabiner, Eugenii A.Invicro LLC, London, England. (author)
  • Gunn, Roger N.Invicro LLC, London, England.;Imperial Coll London, Div Brain Sci, London, England. (author)
  • Ogden, R. ToddColumbia Univ, Dept Psychiat, New York, NY USA.;New York State Psychiat Inst & Hosp, Mol Imaging & Neuropathol Div, New York, NY 10032 USA.;Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. (author)
  • Cervenk, SimonKarolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm Cty Council, Stockholm Hlth Care Serv, SE-17176 Stockholm, Sweden. (author)
  • Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm Cty Council, Stockholm Hlth Care Serv, SE-17176 Stockholm, Sweden.Copenhagen Univ Hosp, Neurobiol Res Unit, Copenhagen, Denmark. (creator_code:org_t)

Related titles

  • In:NeuroImage: ACADEMIC PRESS INC ELSEVIER SCIENCE188, s. 102-1101053-81191095-9572

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