title: Discovery of Radioiodinated Monomeric Anthraquinones as a Novel Class of Necrosis Avid Agents for Early Imaging of Necrotic Myocardium.
abstract: Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All (131)I-anthraquinones showed high affinity to necrotic tissues and (131)I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of (131)I-rhein, which was earlier than that with (131)I-Hyp. Moreover, (131)I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. (131)I-rhein was a more promising "hot spot imaging" tracer for earlier visualization of necrotic myocardium than (131)I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT ((123)I and (99m)Tc) or PET/CT imaging ((18)F and (124)I) of myocardial necrosis.
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Shengwei
authors.initials: S
authors.lastname: Yang
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.|Department of Natural Medicinal Chemistry &National Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jindian
authors.initials: J
authors.lastname: Li
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.|Department of Natural Medicinal Chemistry &National Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
authors.forename: Linwei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Qiaomei
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200127, China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.|Theragnostic Laboratory, Campus Gasthuisberg, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.|Theragnostic Laboratory, Campus Gasthuisberg, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Natural Medicinal Chemistry &National Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000873:Anthracenes; D000880:Anthraquinones / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007457:Iodine Radioisotopes / Q000737:chemistry*; D008297:Male; D051379:Mice; D064847:Multimodal Imaging; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis / Q000503:physiopathology*; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry; D011854:Radiochemistry; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D000873:Anthracenes; D000880:Anthraquinones; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D010569:Perylene; C004965:hypericin