Alzheimer’s disease can involve brain copper dyshomeostasis. We aimed to determine the effect of AD-like pathology on 64Cu trafficking in mice, using positron emission tomography (PET imaging), during 24 hours after intravenous administration of ionic 64Cu (Cu(II) acetate) and 64Cu-GTSM (GTSMH2 = glyoxalbis(thiosemicarbazone)). Copper trafficking was evaluated in 6-8-month-old and 13-15 month-old TASTPM transgenic and wild-type mice, by imaging 0-30 min and 24-25 h after intravenous administration of 64Cu tracer. Regional 64Cu distribution in brains was compared by ex vivo autoradiography to that of amyloid-β plaque. 64Cu-acetate showed uptake in, and excretion through, liver and kidneys. There was minimal uptake in other tissues by 30 minutes, and little further change after 24 h. Radioactivity within brain was focussed in and around the ventricles and was significantly greater in younger mice. 64CuGTSM was taken up in all tissues by 30 min, remaining high in brain but clearing substantially from other tissues by 24 h. Distribution in brain was not localised to specific regions. TASTPM mice showed no major changes in global or regional 64Cu brain uptake compared to wildtype after administration of 64Cu acetate (unlike 64Cu-GTSM) but efflux of 64Cu from brain by 24 h was slightly greater in 6-8 month-old TASTPM mice than in wildtype controls. Changes in copper trafficking associated with Alzheimer’s-like pathology after administration of ionic 64Cu are minor compared to those observed after administration of 64Cu-GTSM. PET imaging with 64Cu could help understand changes in brain copper dynamics in AD and underpin new clinical diagnostic imaging methods.

中文翻译：

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通过正电子发射断层扫描研究阿尔茨海默病小鼠模型中的铜转运：64Cu 乙酸盐和 64CuGTSM 的比较。


阿尔茨海默病可能涉及脑铜稳态失调。我们的目的是使用正电子发射断层扫描（PET 成像），在静脉注射离子 64Cu（醋酸铜 (II)）和 64Cu-GTSM（GTSMH2 = 乙二醛）后 24 小时内，确定 AD 样病理学对小鼠 64Cu 运输的影响。 （缩氨基硫脲））。通过静脉注射 64Cu 示踪剂后 0-30 分钟和 24-25 小时成像，对 6-8 个月大和 13-15 个月大的 TASTPM 转基因小鼠和野生型小鼠的铜转运进行了评估。通过离体放射自显影术将大脑中 64Cu 的区域分布与淀粉样蛋白-β 斑块的分布进行比较。 64Cu-乙酸盐被肝脏和肾脏吸收并通过肝脏和肾脏排泄。 30 分钟时其他组织的吸收量很小，24 小时后几乎没有进一步的变化。大脑内的放射性集中在脑室及其周围，并且在年轻小鼠中明显更高。 64CuGTSM 在 30 分钟内被所有组织吸收，在大脑中保持较高水平，但在 24 小时内从其他组织中基本清除。大脑中的分布并不局限于特定区域。给予 64Cu 醋酸盐后（与 64Cu-GTSM 不同），TASTPM 小鼠的整体或区域 64Cu 脑摄取量与野生型相比没有出现重大变化，但 6-8 个月大的 TASTPM 小鼠 24 小时从脑中流出的 64Cu 略高于对照组。野生型对照。与施用 64Cu-GTSM 后观察到的变化相比，施用离子 64Cu 后与阿尔茨海默病样病理相关的铜运输变化较小。 64Cu PET 成像有助于了解 AD 中脑铜动态的变化，并支持新的临床诊断成像方法。