科研之友
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摘要
Objective: The alpha 7 nicotinic acetylcholine receptors (nAChRs) play a vital role in the pathophysiology of neuropsychiatric diseases such as Alzheimer's disease and depression. However, there is currently no suitable positron emission tomography (PET) or Single-Photon Emission Computed Tomography (SPECT) radioligands for imaging alpha 7 nAChRs in brain. Here our aim is to radiosynthesize a novel SPECT radioligand I-131-CHIBA-1001 for whole body biodistribution study and in vivo imaging of alpha 7 nAChRs in brain. Method: I-131-CHIBA-1001 was radiosynthesized by chloramine-T method. Different conditions of reaction time and temperature were tested to get a better radiolabeling yield. Radiolabeling yield and radiochemical purities of I-131-CHIBA1001 were analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) system. Whole body biodistribution study was performed at different time points post injection of I-131-CHIBA-1001 in KM mice. Monkey subject was used for in vivo SPECT imaging in brain. Result: The radiolabeling yield of I-131-CHIBA-1001 reached 96% within 1.5 similar to 2.0 h at 90 similar to 95 degrees C. The radiochemical purity reached more than 99% after HPLC purification. I-131-CHIBA-1001 was highly stable in saline and fresh human serum in room temperature and 37 degrees C separately. The biodistribution data of brain at 15, 30, and 60 min were 11.05 +/- 1.04%ID/g, 8.8 +/- 0.04%ID/g and 6.28 +/- 1.13%ID/g, respectively. In experimental SPECT imaging, the distribution of radioactivity in the brain regions was paralleled with the distribution of alpha 7 nAChRs in the monkey brain. Moreover, in the blocking SPECT imaging study, the selective alpha 7 nAChR agonist SSR180711 blocked the radioactive uptake in the brain successfully. Conclusion: The CHIBA-1001 can be successfully radiolabeled with I-131 using the chloramine-T method. I-131-CHIBA-1001 can successfully accumulate in the monkey brain and image the alpha 7 acetylcholine receptors. I-131-CHIBA-1001 can be a candidate for imaging alpha 7 acetylcholine receptors, which will be of great value for the diagnosis and treatment of mental diseases.
