J Nucl Med. 2007; 48 (Supplement 2):128P
Radiopharmaceutical Chemistry: New Chemistry-Neurosciences
Alzheimer's and Neurodegenerative Diseases |
Evaluation of a new imaging agent for central nicotinic acetylcholine receptor 
7 subtype
Mikako Ogawa1,
Hideo Tsukada2,
Kentaro Hatano3,
Hiroshi Yamaguchi3,
Junichiro Abe3,
Shingo Nishiyama2,
Takeharu Kakiuchi2,
Hiroyuki Oba2,
Norihiro Harada2,
Yoshitaka Matsushima1,
Takeshi Fuchigami1,
Kengo Ito3 and
Yasuhiro Magata1
1 Hamamatu University School of Medicine, Hamamatsu, Japan; ;
2 Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Japan; ;
3 National Center for Geriatrics and Gerontology, Obu, Japan
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Objectives: Nicotinic acetylcholine receptor (nAChR) 
7 subtype is one of the major nAChR subtypes in the brain. Recent in vitro autoradiographic investigations have suggested that 7 nAChR is implicated in some brain disorders. However, there is no appropriate ligand for in vivo imaging. Recently, we synthesized a novel 7 nAChR ligand, 2-methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester (MeQAA, Ki = 0.17 µM) and radiolabelled this with C-11. In this paper, we evaluated its potential for in vivo imaging of 7 nAChR in the brain with mice and monkeys. Methods: Optically pure isomers of [11C]MeQAA was used in this study. Biodistribution and in vivo receptor blocking studies were undertaken in mice. Dynamic PET scans were performed in conscious monkey using SHR-7700 (Hamamatsu Photonics K.K.). Arterial blood was sampled throughout the scanning period and unmetabolized fraction in plasma was determined. Distribution volume (DV) was estimated by Logan plot analysis. Results: The initial uptake in the mouse brain was high (r-[11C]MeQAA: 7.68, s-[11C]MeQAA: 6.65 %ID/g at 5 min). The clearance of radioactivity of r-[11C]MeQAA was slow in the hippocampus (7 nAChR rich region) and was rather rapid in the cerebellum (7 nAChR poor region). On the other hand, the clearance was faster in s-[11C]MeQAA. The brain uptake of r-[11C]MeQAA was decreased in 32 % in hippocampus by MLA (7 nAChR ligand) treatment. The ondansetron treatments (5HT-3 ligand) had no effect in all brain regions in both isomers. In monkeys, 7 nAChRs are highly distributed in thalamus and cortex and poor in cerebellum. DV of r-[11C]MeQAA was 16.3, 17.0 and 13.8 mL in thalamus, cortex and cerebellum, respectively. In contrast, DV of s-[11C]MeQAA was low, 4.2 mL for thalamus and 3.8 mL for cortex. However, it was also low in cerebellum (3.1 mL). Conclusions: r-[11C]MeQAA was shown to be a promising candidate for imaging 7 nAChR in vivo. The observed difference in each isomer should come from its binding affinities. Further characterization of these tracers and PET analyses are currently underway.
