Biological Safety of Nasal Thallium-201 Administration: A Preclinical Study for Olfacto-scintigraphy
Biological Safety of Nasal Thallium-201 Administration: A Preclinical Study for Olfacto-scintigraphy
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DOI：
10.1269/jrr.10153
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发表时间：
2011-07-01
影响因子：
2
通讯作者：
Miwa, Takaki
中科院分区：
文献类型：
--
作者：
Washiyama, Kohshin;Shiga, Hideaki;Miwa, Takaki
鼻给药铊-201 （(201)Tl）先前已被证明对体内嗅觉神经连通性的评估有用。在进行人体临床试验之前，我们评估了小鼠鼻腔给药（201）Tl的生物学效应，以确定其安全性。（201）正常小鼠（n = 5）在鼻腔右侧给予（201）TlCl（每鼻孔10 μ l (201)TlCl, 74 MBq/ml）后15 min、1、2和9 d，通过高分辨率伽玛相机和x线摄影评估体内Tl摄取。通过观察小鼠对环己亚胺溶液的回避行为，评估正常小鼠（n = 8）在鼻腔两侧给药（201）TlCl后嗅觉上皮厚度（n = 5）。随后，我们在双侧嗅觉神经横断后给药（201）TlCl （n = 4）或生理盐水（n = 4）来评估小鼠双侧嗅觉神经横断后的气味检测能力。（201）正常小鼠鼻腔给予（201）Tl后，鼻腔对Tl的摄取立即减少。经鼻给药（201）Tl对正常小鼠的嗅觉上皮厚度和气味检测能力没有影响。嗅觉神经横断后嗅觉检测能力的恢复在鼻用（201）Tl和生理盐水小鼠之间无显著差异。因此，鼻腔给药（201）Tl诊断创伤性嗅觉损伤在体内没有产生有害的生物学效应。
Nasal administration of thallium-201 ((201)Tl) has previously been shown to be useful for the assessment of olfactory nerve connectivity in vivo. We assessed the biological effects of nasal (201)Tl administration in mice to determine its safety before conducting clinical trials on humans. (201)Tl uptake was evaluated in normal mice (n = 5) in vivo by using a high-resolution gamma camera and radiography 15 min, 1, 2 and 9 d after administration of (201)TlCl to the right side of the nasal cavity (10 mu l (201)TlCl per nostril, 74 MBq/ml). Murine olfactory epithelial thickness (n = 5) was measured 9 d following nasal administration of (201)TlCl We assessed the odor detection ability of normal mice (n = 8) following nasal administration of (201)TlCl to both sides of the nasal cavity, by observing cycloheximide solution avoidance behavior. We subsequently administrated (201)TlCl (n = 4) or saline (n = 4) to both nostrils to assess the odor detection ability of mice following bilateral olfactory nerve transection. (201)Tl uptake by the nasal cavity decreased immediately following nasal administration of (201)Tl in normal mice. Nasal administration of (201)Tl did not affect the olfactory epithelial thickness or the odor detection ability of normal mice. Recovery of odor detection ability following olfactory nerve transection was not significantly different between mice nasally administered with (201)Tl and mice administered with saline. Thus, nasal administration of (201)Tl for the diagnosis of traumatic olfactory impairment did not produce harmful biological effects in vivo.