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

In the early 1990s, 9-(+)-(11)C-dihydrotetrabenazine (9-(+)-(11)C-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-(+)-(11)C-DTBZ analog, 10-(+)-(11)C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-(11)C-DTBZ. 10-(+)-(11)C-DTBZ was obtained by (11)C-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-(+)-(11)C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-(11)C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-(11)C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-(11)C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-(11)C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-(11)C-DTBZ to include dynamic brain distribution in rat brains.