The dopamine transporter (DAT) is closely related to a variety of neurological disorders including Parkinson’s disease (PD) and other neurodegenerative diseases. imaging of DAT with radio-labelled tracers has become a powerful technique in related disorders. The radioiodine-labelled tropane derivative [I]FP-CIT ([I]) is widely used in clinical single photon emission computed tomography (SPECT) imaging as a DAT imaging agent. To develop more metabolically stable DAT radioligands for accurate imaging, this work compared two novel deuterated tropane derivatives ([I]) with non-deuterated tropane derivatives ([I]-). [I]- were obtained in high radiochemical purity (RCP) above 99 % with molar activities of 7.0–10.0 GBq/μmol. The [I] and [I] exhibited relatively higher affinity to DAT (K: 2.0–3.12 nM) than [I] and [I]. Biodistribution results showed that [I] consistently exhibited a higher ratio of the target to non-target (striatum/cerebellum) than [I]. Furthermore, metabolism studies indicated that the metabolic stability of [I] was superior to that of [I]. autoradiography showed that [I] selectively localized on DAT-rich striatal regions and the specific signal could be blocked by DAT inhibitor. These results indicated that [I] might be a potential probe for DAT SPECT imaging in the brain.

中文翻译：

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靶向多巴胺转运蛋白的放射性碘标记氘代托烷衍生物的合成和初步评价

多巴胺转运蛋白（DAT）与多种神经系统疾病密切相关，包括帕金森病（PD）和其他神经退行性疾病。使用放射性标记示踪剂对 DAT 进行成像已成为治疗相关疾病的强大技术。放射性碘标记的托烷衍生物[I]FP-CIT ([I])作为DAT显像剂广泛应用于临床单光子发射计算机断层扫描(SPECT)成像。为了开发代谢更稳定的 DAT 放射性配体以实现精确成像，这项工作将两种新型氘化托烷衍生物 ([I]) 与非氘化托烷衍生物 ([I]-) 进行了比较。 [I]- 的放射化学纯度 (RCP) 高于 99%，摩尔活度为 7.0–10.0 GBq/μmol。 [I] 和 [I] 对 DAT 的亲和力 (K: 2.0–3.12 nM) 比 [I] 和 [I] 表现出相对更高的亲和力。生物分布结果表明，[I] 始终表现出比 [I] 更高的目标与非目标（纹状体/小脑）比率。此外，代谢研究表明[I]的代谢稳定性优于[I]。放射自显影显示[I]选择性地定位于富含DAT的纹状体区域，并且该特定信号可以被DAT抑制剂阻断。这些结果表明 [I] 可能是大脑 DAT SPECT 成像的潜在探针。