Synthesis and biological evaluation of one novel technetium-99m-labeled nitroquipazine derivative as an imaging agent for serotonin transporter.
Imaging of serotonin transporter (SERT) by positron emission tomography (PET) or single-photon emission-computed tomography (SPECT) in humans would provide useful information in diagnosis and therapy of several neurodegenerative and neuropsychiatric disorders. 6-Nitroquipazine is a highly potent and selective inhibitor of the SERT. For the development of new (99m)Tc-labeled 6-nitroquipazine derivatives as SERT imaging agents, novel [N-[2-((3-(4-(6-nitroquinolin-2-yl)piperazin-1-yl)propyl)(2-mercaptoethyl)amino]-acetyl-2-aminoethanethiolato] [(99m)Tc]technetium (V) oxide ((99m)Tc-MAMA-3-PQ) and its rhenium analog were synthesized and characterized. (99m)Tc-MAMA-3-PQ displayed high initial brain uptake (0.52% ID/organ at 2 min post-injection (pi)) and relatively fast washout in mice (0.09% ID/organ at 60 min pi). The regional brain distribution studies in rats showed high-specific binding ratios at 60 min pi. Maximum regional contrast ratio observed for thalamus/cerebellum was 2.94, followed by 2.62 for hypothalamus/cerebellum. These encouraging results lead us to further explore its derivatives as new imaging agents for the SERT in the brain.
Guo
Yunhang
Y
Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
Chen
Xiangji
X
Jia
Hongmei
H
Ji
Xinmin
X
Liu
Boli
B
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011814:Quipazine / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D011814:Quipazine; D013667:Technetium