A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2.
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.
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Zih-Rou
ZR
Huang
PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Chia-Ling
CL
Tsai
PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Ya-Yao
YY
Huang
PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Molecular Imaging Center, National Taiwan University, Taipei, Taiwan.|PET Center, Department of Nuclear Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Chyng-Yann
CY
Shiue
PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Kai-Yuan
KY
Tzen
PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Molecular Imaging Center, National Taiwan University, Taipei, Taiwan.
Ruoh-Fang
RF
Yen
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.|Molecular Imaging Center, National Taiwan University, Taipei, Taiwan.|Center for Innovative Therapeutics Discovery, National Taiwan University, Taipei, Taiwan.
Ling-Wei
LW
Hsin
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D008297:Male; D057054:Molecular Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry; D051381:Rats; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000737:chemistry; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine