Synthesis of [^<11>C]uric acid, using [^<11>C] phosgene, as a possible biomarker in PET imaging for diagnosis of gout
Synthesis of [^<11>C]uric acid, using [^<11>C] phosgene, as a possible biomarker in PET imaging for diagnosis of gout
复制标题
使用[^ 11 C]光气合成[^ 11 C]尿酸，作为诊断痛风的PET成像中的可能生物标志物
DOI：
10.1016/j.bmcl.2011.11.055
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发表时间：
2012
影响因子：
2.7
通讯作者：
Watanabe Y
中科院分区：
文献类型：
--
作者：
Yashio K;Katayama Y;Takashima T;Ishiguro N;Doi H;Suzuki M;Wada Y;Tamai I;Watanabe Y
11C标记尿酸（[11C]1）是一种诊断尿酸相关生活方式疾病的潜在显像剂，通过正电子发射断层扫描（PET）图像分析进行了合成和体内评价。首先，5,6-二氨基尿嘧啶(2)与11C标记的光气（[11C]COCl2）反应合成[11C]1。[11C]1的放射化学产率为37±7%（根据[11C]COCl2进行衰减校正），合成结束时的比放射性为96-152GBq /μmol （n=6）。从轰击结束算起，包括配方在内的放射合成平均时间约为30min，放射化学纯度为bb0 98%。其次，在1,8-二（二甲氨基）萘存在下，以硫酸5,6-二氨基尿嘧啶(3)和[11C] cocl2为原料，优化了[11C]1的合成方法。用该方法合成[11C]1的放射化学产率为36±6%，比放射活性为89-142GBq /μmol，放射化学纯度为98% （n=5）。这使得[11C]1的合成可以重复进行，并且[11C]1的放射化学产率、比放射性、平均合成时间和放射化学纯度与使用2获得的相似。PET研究显示，在正常和高尿酸血症条件下，大鼠四肢放射配体的积累有很大差异。因此，一种高效、便捷的自动合成[11C]1的方法已经被开发出来，并且[11C]1的初步PET评价证实了在高尿酸血症大鼠模型的四肢中放射性积累增加。
The synthesis and in vivo evaluation of11C -labeled uric acid ([11C]1), a potential imaging agent for the diagnosis of urate-related life-style diseases, was performed using positron emission tomography (PET) image analysis. First, the synthesis of [11C]1 was achieved by reacting 5,6-diaminouracil (2) with11C-labeled phosgene ([11C]COCl2). The radiochemical yield of [11C]1 was 37±7% (decay-corrected based on [11C]COCl2) with specific radioactivities of 96–152GBq/μmol at the end of synthesis (n=6). The average time of radiosynthesis from the end of bombardment, including formulation, was about 30min with >98% radiochemical purity. Second, the synthetic approach to [11C]1 was optimized using 5,6-diaminouracil sulfate (3) with [11C]COCl2in the presence of 1,8-bis(dimethylamino)naphthalene. [11C]1 was synthesized in 36±6% radiochemical yield, 89–142GBq/μmol of specific radioactivities, and 98% radiochemical purity by this method (n=5). This allowed the synthesis of [11C]1 to be carried out repeatedly and the radiochemical yield, specific radioactivities, average time of synthesis, and radiochemical purity of [11C]1 were similar to those obtained using 2. PET studies in rats showed large differences in the accumulation of radioligand in the limbs under normal and hyperuricemic conditions. Thus, an efficient and convenient automated synthesis of [11C]1 has been developed, and preliminary PET evaluation of [11C]1 confirmed the increased accumulation of radioactivity in the limbs of a rat model of hyperuricemia.