Single-photon emission computed tomography (SPECT) imaging using intravenous radioactive ligand administration to indirectly evaluate the time-dependent effect of intranasal drugs with poor blood-brain barrier permeability on brain drug distributions in mice was evaluated. The biodistribution was examined using domperidone, a dopamine D2 receptor ligand, as the model drug, with intranasal administration at 0, 15, or 30 min before intravenous [¹²³I]IBZM administration. In the striatum, [¹²³I]IBZM accumulation was significantly lower after intranasal (IN) domperidone administration than in controls 15 min after intravenous [¹²⁵I]IBZM administration. [¹²³I]IBZM SPECT was acquired with intravenous (IV) or IN domperidone administration 15 min before [¹²³I]IBZM, and time–activity curves were obtained. In the striatum, [¹²³I]IBZM accumulation was clearly lower in the IN group than in the control and IV groups. Time–activity curves showed no significant difference between the control and IV groups in the striatum, and values were significantly lowest during the first 10 min in the IN group. In the IN group, binding potential and % of receptor occupancy were significantly lower and higher, respectively, compared to the control and IV groups. Thus, brain-migrated domperidone inhibited D2R binding of [¹²³I]IBZM. SPECT imaging is suitable for research to indirectly explore nose-to-brain drug delivery and locus-specific biological distribution.

中文翻译：

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在小鼠中使用血脑屏障渗透性差的化合物对可能的鼻到脑给药进行间接 SPECT 成像评估

评估了使用静脉内放射性配体给药的单光子发射计算机断层扫描 (SPECT) 成像，以间接评估血脑屏障通透性差的鼻内药物对小鼠脑药物分布的时间依赖性影响。使用多潘立酮（一种多巴胺 D2 受体配体）作为模型药物，在静脉内 [ ¹²³ I]IBZM 给药前 0、15 或 30 分钟鼻内给药，检查生物分布。在纹状体中，[ ¹²³ I]IBZM 在鼻内 (IN) 多潘立酮给药后的蓄积显着低于对照组，在静脉内 [ ¹²⁵ I]IBZM 给药后 15 分钟。[ ^{123I]IBZM SPECT 在 [ 123} I]IBZM前 15 分钟通过静脉内 (IV) 或 IN 多潘立酮给药获得，并获得时间-活性曲线。在纹状体中，IN 组的[ ¹²³ I]IBZM 积累明显低于对照组和IV 组。时间-活动曲线显示，在纹状体中，对照组和 IV 组之间没有显着差异，并且在 IN 组的前 10 分钟内值显着最低。在 IN 组中，与对照组和 IV 组相比，结合潜力和受体占据百分比分别显着降低和升高。因此，脑迁移的多潘立酮抑制 [ ¹²³I]IBZM。SPECT 成像适用于间接探索鼻到脑药物传递和位点特异性生物分布的研究。