ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) is suggested as a promising serotonin transporter (SERT) imaging agent for central nervous system. In this paper, biodistribution studies in rats showed that the initial uptake of 131I-ADAM in the brain was high (1.087%ID at 2 min post-injection), and consistently displayed the highest binding (between 60~240 min post-injection) in hypothalamus, a region known with the highest density of SERT. The specific binding((T/CB)-1) of 131I-ADAM in hypothalamus were 2.94, 3.03 and 3.09 at 60, 120 and 240 min post-injection, respectively. The (T/CB)-1 was significantly blocked by pretreatment with paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug (5HT2A antagonist) Ketanserin, showed no block effect. The rat brain autoradiography and analysis showed that there was a high 131I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94±0.39 to 1.30±0.56 by pretreatment with paroxetine at 60 min post-injection. Blood clearance kinetics was performed in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation is: C=3.6147e-0.0725t + 1.0413e-0.0028t. The thyroid uptake was 0.009% ID and 1.421% ID at 2 min and 120 min post-injection, respectively, suggesting that in vivo deiodination may be the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to humans, assuming a weight of 50kg. These data suggest that 131I-ADAM may be useful for SPECT imaging of SERT binding sites in the brain.
LEI BeiZHU JunqingLU ChunxiongJIANG QuanfuZOU MeifengWANG SongpeiLI XiaominWU Chunying
The synthesis and biodistribution of β-amyloid plaques imaging agent [131I]-2- (4′-dimethylaminophenyl)- 6-iodoimidazo[1,2-α] pyridine ([131I]IMPY) were reported. The chemical structure of the labeling precursor 2-(4′-dimethylaminophenyl)-6-(tributylstannyl)imidazo[1,2-α] pyridine and all its intermediates were verified by IR,HNMR and MS. The radioiodinated compound was prepared using iododestannylation reaction by hydrogen per-oxide. Final radiochemical purity was above 95% determined by TLC. The in vivo biodistribution of [131I]IMPY in normal mice showed excellent brain uptake and washout, indicating this thioflavin-T based small molecular probe has potential for in vivo imaging amyloid deposits.
The synthesis and biological evaluation of serotonin (5-HTB1AB) imaging agent [P131PI]- 4-iodo-N-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-N-pridin-2-yl-benzamide ([P131PI]MPPI ) are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, P1PHNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [P131PI]MPPI in rats displayed high uptake in hippocam-pus and low uptake in cerebellum. The ratio of the uptake of [P131PI]MPPI in hippocampus to that in cerebellum was 2.90 at 30 min post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 min, respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of me-tabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HTB1AB agonist, compared with control. These findings strongly sug-gested that P131PI-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HTB1AB receptor system in animals.
SUN Bai-ShanLU Chun-XiongZOU Mei-FenJIANG Quan-FuWANG Song-PeiLI Xiao-MinCHEN Zheng-PingZHU Jun-QingWU Chun-Ying
