Biodistribution and Radiation Dosimetry of 18 F-FTC-146 in Humans

J Nucl Med. 2017 Dec;58(12):2004-2009. doi: 10.2967/jnumed.117.192641. Epub 2017 Jun 1.

Abstract

The purpose of this study was to assess safety, biodistribution, and radiation dosimetry in humans for the highly selective σ-1 receptor PET agent 18F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one (18F-FTC-146). Methods: Ten healthy volunteers (5 women, 5 men; age ± SD, 34.3 ± 6.5 y) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/MRI examinations were acquired for up to 3 h after injection (357.2 ± 48.8 MBq). Blood samples were collected, and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions of interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry were estimated. Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to 18F-FTC-146 were reported. High accumulation of 18F-FTC-146 was observed in σ-1 receptor-dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose of 18F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range, 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade 18F-FTC-146 were successful. Injection of 18F-FTC-146 is safe, and absorbed doses are acceptable. The potential of 18F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.

Keywords: PET; biodistribution; first-in-human; radiation dosimetry; sigma-1 receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Azepines / adverse effects
  • Azepines / chemical synthesis
  • Azepines / pharmacokinetics*
  • Benzothiazoles / adverse effects
  • Benzothiazoles / chemical synthesis
  • Benzothiazoles / pharmacokinetics*
  • Female
  • Healthy Volunteers
  • Humans
  • Isotope Labeling
  • Magnetic Resonance Imaging
  • Male
  • Multimodal Imaging
  • Radiometry
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptors, sigma / drug effects
  • Receptors, sigma / metabolism
  • Tissue Distribution
  • Whole Body Imaging

Substances

  • 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo(d)thiazol-2(3H)-one
  • Azepines
  • Benzothiazoles
  • Radiopharmaceuticals
  • Receptors, sigma
  • sigma-1 receptor