title: Novel cyclopentadienyl tricarbonyl (99m)tc complexes containing 1-piperonylpiperazine moiety: potential imaging probes for sigma-1 receptors.
abstract: We report the design, synthesis, and evaluation of a series of novel cyclopentadienyl tricarbonyl (99m)Tc complexes as potent σ1 receptor radioligands. Rhenium compounds 3-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)propylcarbonylcyclopentadienyl tricarbonyl rhenium (10a) and 4-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)butylcarbonylcyclopentadienyl tricarbonyl rhenium (10b) possessed high in vitro affinity for σ1 receptors and moderate to high selectivity for σ2 receptors and the vesicular acetylcholine transporter. Biodistribution studies in mice demonstrated high initial brain uptake for corresponding (99m)Tc derivatives [(99m)Tc]23 and [(99m)Tc]24 of 2.94 and 2.13% injected dose (ID)/g, respectively, at 2 min postinjection. Pretreatment of haloperidol significantly reduced the radiotracer accumulation of [(99m)Tc]23 or [(99m)Tc]24 in the brain. Studies of the cellular uptake of [(99m)Tc]23 in C6 and DU145 tumor cells demonstrated a reduction of accumulation by incubation with haloperidol, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (SA4503), or 1,3-di-o-tolyl-guanidine (DTG). Furthermore, blocking studies in C6 glioma-bearing mice confirmed the specific binding of [(99m)Tc]23 to σ1 receptors in the tumor.
authors: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors: Xia
authors: X
authors: Wang
authors: Dan
authors: D
authors: Li
authors: Winnie
authors: W
authors: Deuther-Conrad
authors: Jie
authors: J
authors: Lu
authors: Ying
authors: Y
authors: Xie
authors: Bing
authors: B
authors: Jia
authors: Mengchao
authors: M
authors: Cui
authors: Jörg
authors: J
authors: Steinbach
authors: Peter
authors: P
authors: Brust
authors: Boli
authors: B
authors: Liu
authors: Hongmei
authors: H
authors: Jia
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism; D006220:Haloperidol / Q000493:pharmacokinetics; D008024:Ligands; D008297:Male; D008813:Mice, Inbred ICR; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010879:Piperazines / Q000737:chemistry* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism; D017480:Receptors, sigma / Q000032:analysis / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D000097605:Sigma-1 Receptor
chemical_list: D006220:Haloperidol; D008024:Ligands; D015335:Molecular Probes; D015609:Organotechnetium Compounds; D010879:Piperazines; D017480:Receptors, sigma; D013667:Technetium; D000097605:Sigma-1 Receptor; C078092:1-piperonylpiperazine; C101789:SA 4503