Kilian Hailey I, Kang Homan, Nyayapathi Nikhila, Fukuda Takeshi, Adluru Eeswar, Zhang Huijuan, Quinn Breandan, Xia Jun, Choi Hak Soo, Lovell Jonathan F
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Biomater Sci. 2020 Aug 7;8(15):4199-4205. doi: 10.1039/d0bm00572j. Epub 2020 Jun 9.
The second near-infrared window (NIR-II) beyond 1000 nm has attracted attention for optical contrast imaging in small animals. We sought to assess whether commercially available NIR-II dyes could be easily formulated for this purpose. 13 hydrophobic NIR-II dyes were purchased and screened by formulating them in simple solubilizing agents with established use in humans: propylene glycol, Cremaphor EL, Kolliphor HS15 (HS15), Tween 80, and cyclodextrin. Based on the absorption at 1064 nm (matching the Nd:YAG laser output commonly used in photoacoustic imaging), three of the dyes were further assessed at varying dye and surfactant concentrations. Of these, benzo indole butyl diphenylaminocyclopentene heptamethine (BIBDAH) tetrafluoroborate in HS15 generally showed the most favorable NIR-II character. 1 mg mL BIBDAH in 25% HS15 exhibited a single absorption peak at 1030 nm with a calculated intensity greater than 100, which was relatively stable for weeks in storage. Following intravenous administration to mice, determination of BIBDAH pharmacokinetics was possible by absorption measurements of sampled plasma, revealing a circulating half-life of about one hour. Most of the dye was taken up by the liver. BIBDAH was used in vitro and in vivo as a photoacoustic contrast imaging agent and its accumulation could be detected in subcutaneous tumors in mice. BIBDAH was used for fluorescence imaging of blood vessels in mice, including in the brain (through intact skull), and dye clearance from blood to the liver was visualized. Taken together, this study confirms that accessible, strongly-absorbing dye can readily be formulated for injection by simply dissolving them in biocompatible surfactants and used for high-contrast preclinical optical imaging in the second NIR window.
超过1000 nm的第二个近红外窗口（NIR-II）已引起人们对小动物光学对比成像的关注。我们试图评估市售的NIR-II染料是否能为此目的轻松配制。购买了13种疏水性NIR-II染料，并通过将它们配制在已在人体中确立用途的简单增溶剂中来进行筛选：丙二醇、聚氧乙烯蓖麻油（Cremaphor EL）、聚山梨醇酯HS15（HS15）、吐温80和环糊精。基于在1064 nm处的吸收（与光声成像中常用的Nd:YAG激光输出相匹配），进一步评估了三种染料在不同染料和表面活性剂浓度下的情况。其中，HS15中的苯并吲哚丁基二苯基氨基环戊烯七甲川（BIBDAH）四氟硼酸盐通常表现出最有利的NIR-II特性。25% HS15中1 mg/mL的BIBDAH在1030 nm处呈现单个吸收峰，计算强度大于100，在储存数周内相对稳定。给小鼠静脉注射后，通过对采集的血浆进行吸收测量可以确定BIBDAH的药代动力学，显示循环半衰期约为1小时。大部分染料被肝脏摄取。BIBDAH在体外和体内用作光声对比成像剂，并且可以在小鼠皮下肿瘤中检测到其积累。BIBDAH用于小鼠血管的荧光成像，包括在大脑中（通过完整的颅骨），并且可以观察到染料从血液到肝脏的清除。综上所述，本研究证实，通过将易获得、强吸收的染料简单溶解在生物相容性表面活性剂中，可以很容易地配制用于注射，并用于第二个近红外窗口的高对比度临床前光学成像。
