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Whole body [11C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates

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Abstract

Purpose

Vesicular monoamine transporter type 2 abundance quantified using the radiotracer [11C]-dihydrotetrabenazine (DTBZ) has been used to study diagnosis and pathogenesis of dementia and psychiatric disorders in humans. In addition, it may be a surrogate marker for insulin-producing pancreatic beta cell mass, useful for longitudinal measurements using positron emission tomography to track progression of autoimmune diabetes. To support the feasibility of long-term repeated administrations, we estimate the biodistribution and dosimetry of [11C]-DTBZ in humans.

Methods

Five baboon studies were acquired using a Siemens ECAT camera. After transmission scanning, 165-210 MBq of [11C]-DTBZ were injected, and dynamic whole body emission scans were conducted. Time-activity data were used to obtain residence times and estimate absorbed radiation dose according to the MIRD model.

Results

Most of the injected tracer localized to the liver and the lungs, followed by the intestines, brain, and kidneys. The highest estimated absorbed radiation dose was in the stomach wall.

Conclusions

The largest radiation dose from [11C]-DTBZ is to the stomach wall. This dose estimate, as well as the radiation dose to other radiosensitive organs, must be considered in evaluating the risks of multiple administrations.

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Acknowledgments

The authors are grateful to the imaging team in the Department of Neuroscience for acquiring the whole-body studies. We would like to thank Dr. Michael G. Stabin, PhD for his guidance. This work was supported by grants from US PHS, NIDDK, 5 P30 DK063608-02 (RL), 2 RO1 DK63567-03 (PEH), Telethon.it-JDRF GJT04003 (PEH), and the Columbia University DERC. All experiments were performed in compliance with the laws of the USA and of the City and State of New York, as well with ethics approval by the Institutional Review Board at the New York State Psychiatric Institute.

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Authors and Affiliations

  1. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

    Paul Harris & Rudolph Leibel

  2. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

    Rajan Murthy, Norman Simpson, J. John Mann & Ramin Parsey

  3. Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

    Ronald Van Heertum & J. John Mann

  4. Department of Neuroscience, Division of Brain Imaging, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 42, New York, NY, 10032, USA

    Rajan Murthy, Ronald Van Heertum & J. John Mann

Authors
  1. Rajan Murthy
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  2. Paul Harris
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  3. Norman Simpson
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Correspondence to Rajan Murthy.

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Murthy, R., Harris, P., Simpson, N. et al. Whole body [11C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates. Eur J Nucl Med Mol Imaging 35, 790–797 (2008). https://doi.org/10.1007/s00259-007-0648-2

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  • DOI: https://doi.org/10.1007/s00259-007-0648-2

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