Biological Safety of Nasal Thallium-201 Administration: A Preclinical Study for Olfacto-scintigraphy

Nasal administration of thallium-201 (201Tl) has previously been shown to be useful for the assessment of olfactory nerve connectivity in vivo. We assessed the biological effects of nasal 201Tl administration in mice to determine its safety before conducting clinical trials on humans. 201Tl 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 201TlCl to the right side of the nasal cavity (10μl 201TlCl per nostril, 74MBq/ml). Murine olfactory epithelial thickness (n=5) was measured 9d following nasal administration of 201TlCl. We assessed the odor detection ability of normal mice (n=8) following nasal administration of 201TlCl to both sides of the nasal cavity, by observing cycloheximide solution avoidance behavior. We subsequently administrated 201TlCl (n=4) or saline (n=4) to both nostrils to assess the odor detection ability of mice following bilateral olfactory nerve transection. 201Tl uptake by the nasal cavity decreased immediately following nasal administration of 201Tl in normal mice. Nasal administration of 201Tl 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 201Tl, and mice administered with saline. Thus, nasal administration of 201Tl for the diagnosis of traumatic olfactory impairment did not produce harmful biological effects in vivo.