11C-ORM-13070, a novel PET ligand for brain α2C-adrenoceptors: radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-10

AUTHORS

Pauliina Luoto, Sami Suilamo, Vesa Oikonen, Eveliina Arponen, Semi Helin, Jukka Herttuainen, Johanna Hietamäki, Aila Holopainen, Marita Kailajärvi, Juha M. Peltonen, Juha Rouru, Jukka Sallinen, Mika Scheinin, Jere Virta, Kirsi Virtanen, Iina Volanen, Anne Roivainen, Juha O. Rinne

ABSTRACT

PURPOSE: (11)C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl]-4-(3-methoxy-methylpyridin-2-yl)-piperazine ((11)C-ORM-13070) is a novel PET tracer for imaging of α2C-adrenoceptors in the human brain. Brain α2C-adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer's disease. To validate the use of (11)C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose. METHODS: Radiometabolism was studied in a test-retest setting in six healthy men. After intravenous injection of (11)C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time-activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of (11)C-ORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling. RESULTS: Two radioactive metabolites of (11)C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged (11)C-ORM-13070 decreased from 81 ± 4 % of total radioactivity at 4 min after tracer injection to 23 ± 4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged (11)C-ORM-13070 in arterial plasma were 0.0117 ± 0.0056 min(-1) and 73.6 ± 35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 - 4.2 μSv/MBq. CONCLUSION: (11)C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of (11)C-ORM-13070 was in the same range as that of other (11)C-labelled brain receptor tracers. An injection of 500 MBq of (11)C-ORM-13070 would expose a subject to 2.0 mSv of radiation. This supports the use of (11)C-ORM-13070 in repeated PET scans, for example, in receptor occupancy trials with novel drug candidates. More... »

PAGES

1947-1956

References to SciGraph publications

  • 2007-10. Performance of the new generation of whole-body PET/CT scanners: Discovery STE and Discovery VCT in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00259-014-2782-y

    DOI

    http://dx.doi.org/10.1007/s00259-014-2782-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1003231921

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24838249


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