Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice

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• 作者：Pengjun Zhang^a ; ¹ ; Yuanyuan Yue^a ; ¹ ; Donghui Pan^b ; Runlin Yang^b ; Yuping Xu^b ; Lizhen Wang^b ; Junjie Yan^b ; Xiaotian Li^a ; ^{lixt@zzu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Min Yang^a ; ^b ; ^{yangmin@jsinm.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Melanin ; Pharmacokinetics ; Iron-overload ; Zr-89 ; Radiolabel
• 刊名：Nuclear Medicine and Biology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：43
• 期：9
• 页码：529-533
• 全文大小：430 K

文摘

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 ⁸⁹Zr, a long half-life (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with ⁸⁹Zr directly at pH 5, 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 ⁸⁹Zr-MP was stable in human plasma and PBS for at least 48 h. The half-life of ⁸⁹Zr-MP was about 15.70 ± 1.74 h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that ⁸⁹Zr-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.