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Biodistribution and Radiation Dosimetry of the Glycine Transporter-1 Ligand 11C-GSK931145 Determined from Primate and Human Whole-Body PET

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Abstract

Purpose

11C-GSK931145 is a novel radioligand suitable for imaging the glycine transporter 1 (GlyT-1) in brain. In the present study, human dosimetry is estimated from baboon and human biodistribution data.

Procedures

Three baboons and eight healthy human volunteers underwent whole-body positron emission tomography (PET) scans. Human dosimetry was estimated using three different region-of-interest (ROI) delineation methods that ranged in their complexity and execution time: ROIs drawn on anterior-posterior compressed PET images, on subsamples of the organs, and covering the whole-organ. Residence times for each organ were calculated as the area under the time-activity curves divided by the injected activity. Radiation dose estimates were calculated from organ residence times using the OLINDA/EXM software package.

Results

The overall distribution of activity was similar in baboons and humans. Early scans presented high activity in the liver, and moderate activity in the lungs and kidneys. The principal route of clearance was intestinal and no urinary excretion was observed. The limiting organ with the highest radiation-absorbed dose was the liver. The mean effective dose in humans was 4.02 μSv/MBq (male phantom) and 4.95 μSv/MBq (female phantom) (ROIs drawn on subsamples of the organs). The human effective dose estimated from baboon data was ~15% larger than the effective dose estimated from human data.

Conclusion

Human PET imaging of the glycine transporter-1 with 11C-GSK931145 results in a moderate effective human radiation dose, which allows for multiple PET examinations in the same individual. Among the three methods compared to delineate ROIs, the organ subsampling method shows the best balance between quantitative accuracy and practical application.

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Acknowledgments

The authors would like to thank the GlaxoSmithKline GlyT-1 project team for developing, synthesising, and supplying GSK931145; developing CIB, protocol; conducting preclinical pharmacology, safety evaluations; and providing CMC and regulatory inputs. PET teams of Columbia University (NY, US) and the CRC Molecular Imaging Centre (CRC-CIM) (Barcelona, Spain) are acknowledged for their help in performing the baboon and human PET scans, respectively. Grateful acknowledgment is also made to the staff of Pharmacology Unit of the Institut Municipal d’Investigacions Mèdiques (IMIM) (Barcelona, Spain) for their contribution in the recruitment and care of the healthy volunteers. Finally, our sincere thanks go to all the volunteers who participated in the study.

Conflict of Interest Disclosure

This study was funded by GlaxoSmithKline. J. Passchier, NV. Murthy, RN. Gunn, M. Laruelle and AM. Catafau are GlaxoSmithKline employees.

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Authors and Affiliations

  1. Neurosciences Imaging Group, Molecular Imaging Centre (CRC-CIM), Barcelona Biomedical Research Park, Dr. Aiguader 88, soterrani -1, 08003, Barcelona, Spain

    Santiago Bullich & Antonio Gutiérrez

  2. Department of Psychiatry, Columbia University, New York, USA

    Mark Slifstein, Lawrence S. Kegeles, Jong-Hoon Kim & Xiaoyan Xu

  3. Clinical Imaging Centre, GlaxoSmithKline, London, UK

    Jan Passchier, Roger N. Gunn & Marc Laruelle

  4. Discovery Medicine, Neurosciences CEDD, GlaxoSmithKline, London, UK

    N. Venkatesha Murthy & Ana M. Catafau

  5. Department of Psychiatry, Gachon University of Medicine and Science, Incheon, South Korea

    Jong-Hoon Kim

  6. Department of Engineering Science, University of Oxford, Oxford, UK

    Roger N. Gunn

  7. Division of Neuroscience and Mental Health, Imperial College, London, UK

    Roger N. Gunn

  8. Institut d’Alta Tecnologia (IAT), Barcelona Biomedical Research Park, CRC Corporació Sanitària, Barcelona, Spain

    Raul Herance & Juan Domingo Gispert

  9. Clinical Pharmacology Unit, Institut Municipal d’Investigacions Mèdiques (IMIM), Autonomous University of Barcelona, Barcelona, Spain

    Magí Farré

Authors
  1. Santiago Bullich
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  2. Mark Slifstein
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  3. Jan Passchier
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  4. N. Venkatesha Murthy
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  5. Lawrence S. Kegeles
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  6. Jong-Hoon Kim
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  7. Xiaoyan Xu
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  8. Roger N. Gunn
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  9. Raul Herance
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  10. Juan Domingo Gispert
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  11. Antonio Gutiérrez
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  12. Magí Farré
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  13. Marc Laruelle
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  14. Ana M. Catafau
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Corresponding author

Correspondence to Santiago Bullich.

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Bullich, S., Slifstein, M., Passchier, J. et al. Biodistribution and Radiation Dosimetry of the Glycine Transporter-1 Ligand 11C-GSK931145 Determined from Primate and Human Whole-Body PET. Mol Imaging Biol 13, 776–784 (2011). https://doi.org/10.1007/s11307-010-0398-6

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  • DOI: https://doi.org/10.1007/s11307-010-0398-6

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