A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2

PLoS One. 2016 Sep 9;11(9):e0161295. doi: 10.1371/journal.pone.0161295. eCollection 2016.

Abstract

In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-11C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-11C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ to include dynamic brain distribution in rat brains.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes
  • Chromatography, High Pressure Liquid
  • Male
  • Molecular Imaging*
  • Positron-Emission Tomography*
  • Radiopharmaceuticals* / chemistry
  • Rats
  • Tetrabenazine / analogs & derivatives*
  • Tetrabenazine / chemistry
  • Vesicular Monoamine Transport Proteins / metabolism*

Substances

  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • Vesicular Monoamine Transport Proteins
  • dihydrotetrabenazine
  • Tetrabenazine

Grants and funding

Support was provided by NSC98-2320-B-002-028-MY3.