title: (99m)Tc-Cyclopentadienyl Tricarbonyl Chelate-Labeled Compounds as Selective Sigma-2 Receptor Ligands for Tumor Imaging.
abstract: We have designed and synthesized a series of cyclopentadienyl tricarbonyl rhenium complexes containing a 5,6-dimethoxyisoindoline or a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline pharmacophore as σ2 receptor ligands. Rhenium compound 20a possessed low nanomolar σ2 receptor affinity (K(i) = 2.97 nM) and moderate subtype selectivity (10-fold). Moreover, it showed high selectivity toward vesicular acetylcholine transporter (2374-fold), dopamine D2L receptor, NMDA receptor, opiate receptor, dopamine transporter, norepinephrine transporter, and serotonin transporter. Its corresponding radiotracer [(99m)Tc]20b showed high uptake in a time- and dose-dependent manner in DU145 prostate cells and C6 glioma cells. In addition, this tracer exhibited high tumor uptake (5.92% ID/g at 240 min) and high tumor/blood and tumor/muscle ratios (21 and 16 at 240 min, respectively) as well as specific binding to σ receptors in nude mice bearing C6 glioma xenografts. Small animal SPECT/CT imaging of [(99m)Tc]20b in the C6 glioma xenograft model demonstrated a clear visualization of the tumor at 180 min after injection.
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Radiopharmaceutical Cancer Research/Department of Neuroradiopharmaceuticals, Helmholtz-Zentrum Dresden-Rossendorf , 04318 Leipzig, Germany.
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Medical and Healthy Analytical Center, Peking University , Beijing 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.affiliation: Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Dong
authors.affiliation: Institute of Radiopharmaceutical Cancer Research/Department of Neuroradiopharmaceuticals, Helmholtz-Zentrum Dresden-Rossendorf , 04318 Leipzig, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: Institute of Radiopharmaceutical Cancer Research/Department of Neuroradiopharmaceuticals, Helmholtz-Zentrum Dresden-Rossendorf , 04318 Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jia
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008968:Molecular Conformation; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism*; D012211:Rhenium / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D013667:Technetium / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D017480:Receptors, sigma; C106107:sigma-2 receptor; D012211:Rhenium; D013667:Technetium