In vivo evaluation of P-glycoprotein modulation of 8 PET radioligands used clinically

Kiichi Ishiwata, Kazunori Kawamura, Kazuhiko Yanai, N. Harry Hendrikse

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


P-glycoprotein (P-gp) regulates the ability of endogenous and exogenous compounds to cross the blood-brain barrier. We investigated whether PET tracers used clinically for studying brain function are affected by P-gp. Methods: Modulation of 8 radioligands by P-gp was assayed in mice by evaluating the effect of treatment with cyclosporine A (CsA) on uptake into the brain (assay 1) and the effect of treatment with a cold ligand of the corresponding radioligand on uptake of 11C-verapamil, a representative radioligand for P-gp (assay 2). Brain-to-blood ratios were also examined as the other index to correct the delivery of radioligands. The radioligands investigated were 11C-TMSX (adenosine A2A receptor), 11C-MPDX (adenosine A1 receptor), 11C-PK11195 (peripheral benzodiazepine receptor), 11C-flumazenil (central benzodiazepine receptor), 11C-raclopride (dopamine D2-like receptor), 11C-pyrilamine (histamine H1 receptor), 11C-PIB (amyloid plaque), and 11C-donepezil (acetylcholine esterase). Results: In assay 1, CsA treatment increased both the uptake and the brain-to-blood ratio of 11C-TMSX, 11C-MPDX, 11C-flumazenil, and 11C-donepezil among the 8 radioligands. In assay 2, in which 4 cold ligands were examined, cold verapamil slightly increased the brain-to-blood ratio of 11C-verapamil, but TMSX, MPDX, and MPPF did not increase either parameter. Conclusion: Assay 1 was suitable for evaluating the P-gp modulation of radioligands. Among the 8 radioligands investigated, 11C-TMSX, 11C-MPDX, 11C-flumazenil, and 11C-donepezil were modulated by P-gp.

Original languageEnglish
Pages (from-to)81-87
Number of pages7
JournalJournal of Nuclear Medicine
Issue number1
Publication statusPublished - 2007 Jan 1


  • Cyclosporine A
  • Neuroreceptor
  • P-glycoprotein
  • PET radioligand

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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