Li Xiaomin, Chen Zhengping, Tang Jie, Liu Chunyi, Zou Pei, Huang Hongbo, Tan Cheng, Yu Huixin
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, P. R. China.
Arch Pharm (Weinheim). 2014 May;347(5):313-9. doi: 10.1002/ardp.201300307. Epub 2014 Feb 3.
In this study, we synthesized a new carbon-11-labeled radiotracer, 10-(11) C-dihydrotetrabenazine (10-(11) C-DTBZ), and evaluated its potential as a vesicular monoamine transporter 2 (VMAT2) radioligand. The radiolabeled precursor 10-O-desmethyl-dihydrotetrabenazine (10-O-desmethyl-DTBZ) was prepared with a six-step reaction using 3-methoxy-4-benzyloxybenzaldehyde as starting material. 10-(11) C-DTBZ was synthesized by heating 1.0 mg of 10-hydroxy precursor and (11) C-methyl iodide in the presence of 0.3 mL of dimethyl sulfoxide and 4.0 µL of 3 N KOH at room temperature for 3 min. After purification by solid phase extraction using an alumina Sep-Pak cartridge, the final 10-(11) C-DTBZ product was obtained with a radiochemical purity of >99% and an uncorrected radiochemical yield of 18-26% (end of bombardment (EOB), n = 6). The overall synthesis time was approximately 20 min from the EOB to release of the product for quality control. Using small-animal positron emission tomography (microPET), the striatum of normal rats was found to exhibit symmetrical labeling (STR /STL = 0.98 ± 0.05, n = 3) and the highest uptake of radioactivity (striatum/cerebellum, ST/CB = 2.89 ± 0.31 at 30-60 min, n = 3). In contrast, rats with 6-hydroxydopamine unilateral lesions yielded asymmetrical striatal images with a higher 10-(11) C-DTBZ concentration on the unlesioned side (STunlesioned /CB = 2.53 ± 0.18, at 30-60 min, n = 3) compared with the lesioned side (STlesioned /CB = 1.26 ± 0.10, n = 3). These results suggest that 10-(11) C-DTBZ may represent a promising PET radiotracer for imaging VMAT2.
在本研究中，我们合成了一种新的碳-11标记放射性示踪剂10-(11)C-二氢丁苯那嗪(10-(11)C-DTBZ)，并评估了其作为囊泡单胺转运体2(VMAT2)放射性配体的潜力。以3-甲氧基-4-苄氧基苯甲醛为起始原料，通过六步反应制备放射性标记前体10-O-去甲基二氢丁苯那嗪(10-O-去甲基-DTBZ)。在室温下，将1.0 mg的10-羟基前体与(11)C-甲基碘在0.3 mL二甲基亚砜和4.0 μL 3 N氢氧化钾存在下加热3分钟，合成10-(11)C-DTBZ。使用氧化铝Sep-Pak柱进行固相萃取纯化后，获得最终的10-(11)C-DTBZ产物，其放射化学纯度>99%，未校正的放射化学产率为18-26%(轰击结束(EOB)，n = 6)。从EOB到产品释放进行质量控制的总合成时间约为20分钟。使用小动物正电子发射断层扫描(microPET)，发现正常大鼠的纹状体呈现对称标记(STR/STL = 0.98±0.05，n = 3)，放射性摄取最高(纹状体/小脑，30-60分钟时ST/CB = 2.89±0.31，n = 3)。相比之下，单侧6-羟基多巴胺损伤的大鼠产生不对称的纹状体图像，在未损伤侧10-(11)C-DTBZ浓度更高(30-60分钟时ST未损伤/CB = 2.53±0.18，n = 3)，而损伤侧(ST损伤/CB = 1.26±0.10，n = 3)。这些结果表明，10-(11)C-DTBZ可能是一种有前景的用于VMAT2成像的PET放射性示踪剂。
