Zou Jing
Department of Otolaryngology-Head and Neck Surgery, Center for Otolaryngology-Head & Neck Surgery of Chinese PLA, Changhai Hospital, Second Military Medical University, Shanghai, China.
Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Tampere, Finland.
J Otol. 2015 Dec;10(4):136-142. doi: 10.1016/j.joto.2016.01.005. Epub 2016 Jan 29.
Postaurical injection of therapeutics was recently applied in clinical practice to treat inner ear diseases based on supposed existence of a direct channel from the postaurical area to the inner ear. Doubting on the associated reports and aiming to provide evidence on the inner ear uptake mechanism, the present study tracked the dynamic distribution of gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) in rat inner ears after postaurical injection using MRI. A targeted tympanic medial wall delivery was utilized as control. The results showed that, at the early time points after postaurical injection, Gd-DOTA distributed mainly in tissues surrounding the bulla, temporal bone and skull and neck space. In the inner ear, there was gradual uptake of Gd-DOTA on both the ipsilateral and contralateral sides with equal signal intensities. There was no sign of direct channel carrying the agent from the postaurical area to the inner ear. Targeted tympanic medial wall delivery induced significantly greater uptake of Gd-DOTA in the inner ear than did postaurical injection. At 30 min post-administration, targeted tympanic medial wall delivery yielded 4.6-folds higher signal intensity than did postaurical injection. The total dose of Gd-DOTA delivered by the targeted tympanic medial wall approach was only 0.1% of that delivered by postaurical injection. In conclusion, postaurical injection is a systemic administration, which is similar to hypodermic injection, rather than a focal delivery method. By contraries, targeted tympanic medial wall delivery induces fast and abundant uptake of Gd-DOTA in the ipsilateral inner ear without significant distribution in unwanted areas.
基于耳后区域与内耳之间可能存在直接通道的假设，耳后注射治疗药物最近被应用于临床实践以治疗内耳疾病。由于对相关报道存疑，并旨在为内耳摄取机制提供证据，本研究使用磁共振成像（MRI）追踪了大鼠耳后注射钆-四氮杂环十二烷四乙酸（Gd-DOTA）后内耳中的动态分布情况。以靶向鼓室内侧壁给药作为对照。结果显示，耳后注射后的早期时间点，Gd-DOTA主要分布在鼓泡、颞骨以及头颅和颈部间隙周围的组织中。在内耳中，同侧和对侧均有Gd-DOTA的逐渐摄取，信号强度相等。没有迹象表明存在从耳后区域到内耳的携带该药物的直接通道。靶向鼓室内侧壁给药在内耳中诱导的Gd-DOTA摄取明显多于耳后注射。给药后30分钟，靶向鼓室内侧壁给药产生的信号强度比耳后注射高4.6倍。靶向鼓室内侧壁给药方法所输送的Gd-DOTA总剂量仅为耳后注射所输送剂量的0.1%。总之，耳后注射是一种全身给药方式，类似于皮下注射，而非局部给药方法。相反，靶向鼓室内侧壁给药可诱导同侧内耳快速且大量摄取Gd-DOTA，且在非靶区域无明显分布。
