title: Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice.
abstract: Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with (89)Zr, a long half-life (78.4h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with (89)Zr directly at pH5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The (89)Zr-MP was stable in human plasma and PBS for at least 48h. The half-life of (89)Zr-MP was about 15.70±1.74h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that (89)Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy.
authors.affiliation: School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, 450000, China.
authors.forename: Pengjun
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, 450000, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Pan
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Runlin
authors.initials: R
authors.lastname: Yang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yan
authors.affiliation: School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, 450000, China. Electronic address: lixt@zzu.edu.cn.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, 450000, China; Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China. Electronic address: yangmin@jsinm.org.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D004355:Drug Stability; D006207:Half-Life; D019190:Iron Overload / Q000000981:diagnostic imaging / Q000378:metabolism*; D007553:Isotope Labeling; D008543:Melanins / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D053758:Nanoparticles; D049268:Positron-Emission Tomography; D011868:Radioisotopes; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: D008543:Melanins; D011868:Radioisotopes; D015040:Zirconium
keywords: Iron-overload; Melanin; Pharmacokinetics; Radiolabel; Zr-89