- 期刊
碘－123-IMPY製備與生物特性研究
Preparation and Biological Characterization of 123I-IMPY
摘要
背景：阿茲海默氏症(Alzheimer's disease; AD)隨著科技的發達，罹患率也日愈提升。在臨床的病理診斷方式即是在觀察腦中乙型類澱粉質(β-amyloid; Aβ)蛋白的沈積，這也是AD最明顯的臨床徵兆。在核醫方面針對其病理現象所延伸的核醫藥物，如Thioflavin-T類衍生物可與腦中Aβ蛋白形成鍵結。本研究製備碘－123-IMPY(6-iodo-2-(4'-dimethylamino-) phenyl-imidazo [1,2-]a]pyridine)，並探討其成爲診斷阿玆海默氏症核醫藥物的可行性。 方法：本研究以脫錫碘化反應方式將碘－123標幟在前趨物SnMPY上，並利用放射性薄層色層分析法進行放射化學純度分析。以Tg2576基因轉殖鼠及同品系正常B6鼠進行體外自動輻射顯影試驗、體內microSPECT造影試驗、體表外自動輻射顯影試驗，並以正常B6鼠進行生物體分佈試驗。 結果：Radio-HPLC與radio-TLC證明本研究製備碘－123-IMPY之高放射化學純度（製備復0小時＞95%; 3小時爲92.9%）。體外自動輻射顯影試驗結果發現Tg2576基因轉殖鼠在海馬迴與前皮質層的碘－123-IMPY攝取分別爲2.04±0.37倍與2.12±0.47倍高於對照鼠。體內microSPECT造影結果發現 Tg2576基因轉殖鼠腦部碘－123-IMPY結合無論是在周遭肌肉層或是與參考位置比對均明顯高於對照鼠。體表外自動輻射顯影試驗結果也顯示Tg2576基因轉殖鼠在海馬迴與前皮質層的碘－123-IMPY結合分別爲2.04±0.33與2.19±0.22倍高於對照鼠。生物體分佈試驗結果發現注射復30分鐘腦部累積積聚量可達到最高。 結論：碘－123-IMPY可成爲偵測阿玆海默氏症腦Aβ沈積的核醫藥物。
並列摘要
Background: Loss of neuronal synaptic density and synapse number represent another invariant feature of the disease that appears to precede overt neuronal degeneration. Alzheimer's disease (AD) is the most common form of dementia affecting a large number of patients in the older population. Accumulation of β-amyloid (Aβplaques in the brain is a characteristic neuropathological event to Alzheimer's disease (AD). There are several radioactive ligands developed for in vivo imaging of Aβ plaques. Herein, we reported the preparation of an 123I-labeled Thioflavin-T derivative IMPY [6-iodo-2-(4'-dimethylamino-) phenyl-imidazo [1,2-a]pyridine] and biologically evaluated its potential for imaging Aβplaques in the brain. Methods: 123I-IMPY was prepared by using a typical oxidative iododestannylation with the SnMPY precursor. The radiochemical purity was checked by radio-TLC method. Tg2576 transgenic mice and normal B6 mice were used for in vitro and ex vivo autoradiography, and in vitro microSPECT imaging study. The distribution of 123I-IMPY was studied on normal B6 mice. Results: High radiochemical purity of prepared 123I-IMPY was confirmed by radio-TLC (＞95% at 0 h, 92.9% at 3 h post-preparation). Results of in vitro autoradiography revealed that 123I-IMPY uptakes in hippocampus and frontal cortex of Tg2576 mice were 2.04±0.37 and 2.12±0.47 fold, respectively, higher than control mice. In vivo microSPECT images showed the uptake ratio between brain region to the muscle and reference region in Tg2576 mice was higher than control mice. Results of ex vivo autoradiography demonstrated that 123I-IMPY bindings in hippocampus and frontal cortex of Tg2576 mice were 2.04±0.33 and 2.19±0.22 fold, respectively, higher than control mice. The maximal brain uptake was found at 30 min after intravenous injection of 123I-IMPY. Conclusion: 123I-IMPY is potential for tracing Aβ plaques in brains of Alzheimer's disease patients.