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

• Published in: PloS one 2016-09, Vol.11 (9), p.e0161295-e0161295
• Main Authors: Huang, Zih-Rou, Tsai, Chia-Ling, Huang, Ya-Yao, Shiue, Chyng-Yann, Tzen, Kai-Yuan, Yen, Ruoh-Fang, Hsin, Ling-Wei
• Format: Article
• Language: English
• Subjects: Amphetamines; Animals; Biology and Life Sciences; Brain; Brain - diagnostic imaging; Brain - metabolism; Carbon; Carbon Radioisotopes; Cerebellum; Chromatography, High Pressure Liquid; Dopamine; Emissions; Hospitals; Imaging; Insurance claims; Laboratory animals; Male; Medical imaging; Medicine and Health Sciences; Methylation; Molecular Imaging; Monoamine transporter; Neostriatum; Nervous system diseases; Neurodegenerative diseases; Neuroimaging; Nuclear medicine; People and Places; Pharmacy; Physical Sciences; Positron emission; Positron emission tomography; Radiochemistry; Radiopharmaceuticals - chemistry; Rats; Research and Analysis Methods; Sodium hydroxide; Studies; Tetrabenazine - analogs & derivatives; Tetrabenazine - chemistry; Tomography; Vesicular amine transporter; Vesicular Monoamine Transport Proteins - metabolism; Vesicular monoamine transporter 2
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161295

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.