title: Efficient method for iodine radioisotope labeling of cyclooctyne-containing molecules using strain-promoted copper-free click reaction.
abstract: Herein we report an efficient method for iodine radioisotope labeling of cyclooctyne-containing molecules using copper-free click reaction. For this study, radioiodination using the tin precursor 2 was carried out at room temperature to give (125)I-labeled azide ([(125)I]1) with high radiochemical yield (85%) and excellent radiochemical purity. Dibenzocyclooctyne (DBCO) containing cRGD peptide and gold nanoparticle were labeled with [(125)I]1 at 37°C for 30min to give triazoles with good radiochemical yields (67-95%). We next carried out tissue biodistribution study of [(125)I]1 in normal ICR mice to investigate the level of organ accumulation which needs to be considered for pre-targeted in vivo imaging. Large amount of [(125)I]1 distributed rapidly in liver and kidney from bloodstream and underwent rapid renal and hepatobiliary clearance. Moreover [(125)I]1 was found to be highly stable (>92%) in mouse serum for 24h. Therefore [(125)I]1 could be used as a potentially useful radiotracer for pre-targeted imaging. Those results clearly indicated that the present radiolabeling method using copper free click reaction would be quite useful for both in vitro and in vivo labeling of DBCO group containing molecules with iodine radioisotopes.
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea. Electronic address: jeonj@kaeri.re.kr.
authors.forename: Jongho
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: Jung Ae
authors.initials: JA
authors.lastname: Kang
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: Ha Eun
authors.initials: HE
authors.lastname: Shim
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: You Ree
authors.initials: YR
authors.lastname: Nam
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: Seonhye
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea; Department of Radiation Biotechnology and Applied Radioisotope Science, Korea University of Science and Technology, Deajeon 305-350, Republic of Korea. Electronic address: parksh@kaeri.re.kr.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Park
mesh_terms: D000818:Animals; D001386:Azides / Q000737:chemistry*; D057930:Click Chemistry; D034242:Cyclooctanes / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: D001386:Azides; D034242:Cyclooctanes; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D006046:Gold; C047981:arginyl-glycyl-aspartic acid
keywords: Bioorthogonal reaction; Copper-free click reaction; In vivo imaging; Iodine radioisotope; Radiolabeling