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Whole-body distribution and metabolism of [N-methyl-11C](R)-1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinolinecarboxamide in humans; an imaging agent for in vivo assessment of peripheral benzodiazepine receptor activity with positron emission tomography

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Abstract

Purpose

11C-PK11195 is a radiopharmaceutical for in vivo assessment of peripheral benzodiazepine receptor (PBR) activity using PET. We sought to clarify the metabolic fate of 11C-PK11195 in a test–retest setting using radio-HPLC in comparison with radio-TLC, and the whole-body distribution in humans.

Materials and methods

In order to evaluate the reproducibility of radio-HPLC metabolite analyses, ten patients with Alzheimer’s disease (AD) underwent two successive 11C-PK11195 examinations on separate days. For comparison of different analytical methods, plasma samples from seven patients were also analysed by radio-TLC. In addition, we evaluated the whole-body distribution of 11C-PK11195 and its uptake in the brain.

Results

The level of unmetabolized 11C-PK11195 decreased slowly from 96.3 ± 1.6% (mean±SD) at 5 min to 62.7 ± 8.3% at 40 min after injection. Large individual variation was observed in the amount of plasma 11C-PK11195 radiometabolites. The whole-body distribution of 11C-PK11195 showed the highest radioactivity levels in urinary bladder, adrenal gland, liver, salivary glands, heart, kidneys, and vertebral column. In addition, the hip bone and breast bone were clearly visualized by PET. In patients with AD, 11C-PK11195 uptake in the brain was the highest in the basal ganglia and thalamus, followed by the cortical grey matter regions and the cerebellum. Low 11C-PK11195 uptake was observed in the white matter.

Conclusion

Our results indicate that 11C-PK11195 is eliminated both through the renal and hepatobiliary systems. Careful analysis of plasma metabolites is required to determine the accurate arterial input function for quantitative PET measurement.

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Acknowledgments

The authors thank the staff of the Turku PET Centre for performing PET imaging. Henri Sipilä is thanked for technical assistance in the clinical laboratory measurements. This study was financially supported by Turku University Hospital (EVO 13856) and Turku Imanet, GE Healthcare Medical Diagnostics, Turku, Finland.

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Authors and Affiliations

  1. Turku PET Centre, Turku University Hospital, FI-20521, Turku, Finland

    Anne Roivainen, Jussi Hirvonen, Vesa Oikonen, Pauliina Virsu, Tuula Tolvanen & Juha O. Rinne

  2. Radiopharmaceutical Chemistry Laboratory, University of Turku, FI-20500, Turku, Finland

    Kjell Någren

  3. Turku Imanet, GE Healthcare Medical Diagnostics, Turku, Finland

    Juha O. Rinne

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  1. Anne Roivainen
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  2. Kjell Någren
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  4. Vesa Oikonen
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Correspondence to Anne Roivainen.

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Roivainen, A., Någren, K., Hirvonen, J. et al. Whole-body distribution and metabolism of [N-methyl-11C](R)-1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinolinecarboxamide in humans; an imaging agent for in vivo assessment of peripheral benzodiazepine receptor activity with positron emission tomography. Eur J Nucl Med Mol Imaging 36, 671–682 (2009). https://doi.org/10.1007/s00259-008-1000-1

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  • DOI: https://doi.org/10.1007/s00259-008-1000-1

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