論文種別 | 原著(症例報告除く) |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | Radioiodinated peptide probe for selective detection of oxidized low density lipoprotein in atherosclerotic plaques |
掲載誌名 | 正式名:NUCLEAR MEDICINE AND BIOLOGY ISSNコード:0969-8051 |
出版社 | ELSEVIER SCIENCE INC |
巻・号・頁 | 40(1),pp.97-103 |
著者・共著者 | Kantaro Nishigori,Takashi Temma,Keiko Yoda,Satoru Onoe,Naoya Kondo,Masashi Shiomi,Masahiro Ono,Hideo Saji |
発行年月 | 2013/01 |
概要 | Introduction: Despite the significant effort in developing radioprobes for atherosclerosis, few have low molecular weight. Oxidized LDL (OxLDL), a highly proinflammatory and proatherogenic factor that is abundant in atherosclerotic plaques, plays a pivotal role in plaque destabilization, which makes OxLDL a relevant probe target. We developed a radioiodinated short peptide, AHP7, as a low molecular weight probe for specific OxLDL imaging and evaluated its utility using myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI). Methods: [I-125]AHP7 was designed and synthesized based on the sequence of Asp-hemolysin, an OxLDL binding protein extracted from Aspergillus fumigants. In vitro binding studies with OxLDL having varying degrees of oxidation were performed. Radioactivity accumulation in the aorta was measured 30 min post-administration in rabbits. Autoradiography and histological studies were performed using serial aorta sections. A radioiodinated scrambled peptide ([I-125]AHP scramble) was used as a negative control. Results: [I-125]AHP7 bound to OxLDL in proportion to the degree of oxidation (R = C.91, P<0.0001) and was inhibited by unlabeled AHP7 in a concentration-dependent manner. The aorta accumulation level and aorta/blood and aorta/muscle ratios of [I-125]AHP7 in WHHLMI were 2.8-, 1.3- and 1.8-fold higher, respectively, than those in control rabbits (P<0.001). Co-administration of AHP7 significantly reduced [I-125]AHP7 radioactivity in aorta sections (P<0.0001). Regional radioactivity levels in the aorta sections showed nonuniformity but similarity to the immunohistochemical OxLDL density. Conclusions: The potential of radioiodinated AHP7 for selectively imaging OxLDL was demonstrated both in vitro and in vivo. (C) 2013 Elsevier Inc. All rights reserved. |
DOI | 10.1016/j.nucmedbio.2012.08.002 |
PMID | 23157986 |