Purpose

[¹²³I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous injection, [¹²³I]I-FP-CIT is metabolized for a small part by the enzyme CYP3A4, leading to the formation of [¹²³I]I-nor-β-CIT. [¹²³I]I-nor-β-CIT passes the blood-brain barrier and has a very high affinity for the serotonin transporter (SERT). The SERT is expressed in the striatum and cortical areas. So, at least theoretical, the use of frequently used CYP3A4 inhibitors (like amiodarone) may influence the specific to non-specific striatal [¹²³I]I-FP-CIT ratio. Here we tested this novel hypothesis.

Methods

Using a retrospective design, we determined the specific to non-specific striatal [¹²³I]I-FP-CIT ratio (using BRASS software) in 6 subjects that were using an CYP3A4 inhibitor and 18 matched controls. Only subjects were included with a normal rated [¹²³I]I-FP-CIT SPECT scan, and all participants were scanned on the same brain-dedicated SPECT system.

Results

The specific to non-specific (assessed in the occipital cortex) striatal [¹²³I]I-FP-CIT binding ratio was significantly higher in CYP3A4 users than in the control group (3.52 ± 0.33 vs. 2.90 ± 0.78, p < 0.001).

Conclusion

Our preliminary data suggest that the use of CYP3A4 inhibitors may influence striatal [¹²³I]I-FP-CIT binding ratios. This information, when reproduced in larger studies, may be relevant for studies in which quantification of [¹²³I]I-FP-CIT SPECT imaging is used for diagnostic or research purposes.

中文翻译：

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CYP3A4 抑制剂可能影响 [123I]I-FP-CIT SPECT 扫描的定量

目的

[ ¹²³ I]I-FP-CIT SPECT 是一种成像工具，支持诊断以黑质纹状体多巴胺能变性为特征的帕金森综合征。静脉注射后，[ ¹²³ I]I-FP-CIT的一小部分被CYP3A4酶代谢，导致形成[ ¹²³ I]I-nor-β-CIT。 [ ¹²³ I]I-nor-β-CIT 可穿过血脑屏障，并且与血清素转运蛋白 (SERT) 具有非常高的亲和力。 SERT 在纹状体和皮质区域表达。因此，至少理论上，常用 CYP3A4 抑制剂（如胺碘酮）的使用可能会影响特异性与非特异性纹状体 [ ¹²³ I]I-FP-CIT 比率。在这里，我们测试了这个新颖的假设。

方法

通过回顾性设计，我们确定了6 名使用 CYP3A4 抑制剂的受试者和 18 名匹配对照者的特异性与非特异性纹状体 [ ¹²³ I]I-FP-CIT 比率（使用 BRASS 软件）。仅受试者接受正常评级的[ ¹²³ I]I-FP-CIT SPECT 扫描，并且所有参与者均在同一脑部专用 SPECT 系统上进行扫描。

结果

CYP3A4 用户中特异性与非特异性（在枕叶皮质中评估）纹状体 [ ¹²³ I]I-FP-CIT 结合比率显着高于对照组（3.52 ± 0.33 与 2.90 ± 0.78，p  < 0.001） 。

结论

我们的初步数据表明，CYP3A4 抑制剂的使用可能会影响纹状体 [ ¹²³ I]I-FP-CIT 结合比率。当在更大的研究中重现时，该信息可能与使用 [ ¹²³ I]I-FP-CIT SPECT 成像的量化用于诊断或研究目的的研究相关。