Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.
Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.
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DOI：
10.1371/journal.pone.0084335
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Odani A
中科院分区：
文献类型：
--
作者：
Ogawa K;Ishizaki A;Takai K;Kitamura Y;Kiwada T;Shiba K;Odani A
68Ga（T 1/2 = 68 分钟，一种发生器产生的核素）作为临床正电子发射断层扫描（PET）的放射性核素具有巨大的潜力。由于聚谷氨酸和聚天冬氨酸对羟基磷灰石具有高亲和力，为了开发用于PET的新型骨靶向68Ga标记骨显像剂，我们使用1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）作为螯合位点和不同长度的共轭天冬氨酸肽。随后，我们将易于处理的 67Ga 的 Ga 配合物 Ga-DOTA-(Asp)n (n = 2、5、8、11 或 14) 与之前描述的 67Ga-DOTA 配合物共轭双膦酸盐 67Ga-DOTA-Bn-SCN-HBP 进行了比较。采用基于Fmoc的固相法合成DOTA-(Asp)n后，与67Ga形成络合物，经HPLC纯化后得到67Ga-DOTA-(Asp)n，其放射化学纯度超过95%。在羟基磷灰石结合测定中，67Ga-DOTA-(Asp)n 的结合率随着缀合天冬氨酸肽长度的增加而增加。此外，在生物分布实验中，67Ga-DOTA-(Asp)8、67Ga-DOTA-(Asp)11和67Ga-DOTA-(Asp)14在骨中表现出高积累（分别为10.5±1.5、15.1±2.6和12.8±1.7% ID/g），但注射后60分钟在其他组织中几乎观察不到。虽然67Ga-DOTA-(Asp)n的骨积累低于67Ga-DOTA-Bn-SCN-HBP，但67Ga-DOTA-(Asp)n的血液清除速度更快。因此，67Ga-DOTA-(Asp)11和67Ga-DOTA-(Asp)14的骨/血液比率与67Ga-DOTA-Bn-SCN-HBP相当。总之，这些数据为用于诊断骨转移等骨疾病的 68Ga-PET 示踪剂的药物设计提供了有用的见解。
68Ga (T 1/2 = 68 min, a generator-produced nuclide) has great potential as a radionuclide for clinical positron emission tomography (PET). Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting 68Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Asp)n (n = 2, 5, 8, 11, or 14) with easy-to-handle 67Ga, with the previously described 67Ga-DOTA complex conjugated bisphosphonate, 67Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Asp)n by a Fmoc-based solid-phase method, complexes were formed with 67Ga, resulting in 67Ga-DOTA-(Asp)n with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of 67Ga-DOTA-(Asp)n increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, 67Ga-DOTA-(Asp)8, 67Ga-DOTA-(Asp)11, and 67Ga-DOTA-(Asp)14 showed high accumulation in bone (10.5±1.5, 15.1±2.6, and 12.8±1.7% ID/g, respectively) but were barely observed in other tissues at 60 min after injection. Although bone accumulation of 67Ga-DOTA-(Asp)n was lower than that of 67Ga-DOTA-Bn-SCN-HBP, blood clearance of 67Ga-DOTA-(Asp)n was more rapid. Accordingly, the bone/blood ratios of 67Ga-DOTA-(Asp)11 and 67Ga-DOTA-(Asp)14 were comparable with those of 67Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of 68Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases.
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影响因子：
6.2
作者：
Kasugai, S;Fujisawa, R;Ohya, K
通讯作者：
Ohya, K
影响因子：
4.7
作者：
Ogawa, K;Mukai, T;Saji, H
通讯作者：
Saji, H
影响因子：
2.6
作者：
BUDD, RS;HODGSON, GS;HARE, WSC
通讯作者：
HARE, WSC
DOI：
10.1039/b908652h
发表时间：
2009-08-28
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Torres Martin de Rosales R;Finucane C;Mather SJ;Blower PJ
通讯作者：
Blower PJ
影响因子：
4.7
作者：
de Rosales, Rafael Torres Martin;Finucane, Ciara;Blower, Philip J.
通讯作者：
Blower, Philip J.