Applications of "Hot" and "Cold" Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging
Applications of "Hot" and "Cold" Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging
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DOI：
10.1002/tcr.201500292
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发表时间：
2016-06-01
期刊：
影响因子：
6.6
通讯作者：
Pascu, Sofia I.
中科院分区：
文献类型：
--
作者：
Cortezon-Tamarit, Fernando;Sarpaki, Sophia;Pascu, Sofia I.
配位化学在分子成像中的应用是近10年来研究的热点。特别地，由于使用（64）CuATSM [铜（二乙酰基-双（N4-甲基氨基硫脲））]的PET（正电子发射断层扫描）对缺氧肿瘤的体内成像成功，双（氨基硫脲）金属络合物在分子成像中的应用主要集中在具有脂肪族主链的化合物上。该化合物在21（st）世纪的第一个十年期间进入美国和英国的临床试验，用于成像头颈部肿瘤中的缺氧。在合成双（缩氨基硫脲）的过程中，配体骨架被取代为芳族基团，再加上环外N的官能化，打开了使用相应的金属络合物作为多模态成像剂的可能性，无论是在体外用于光学检测，还是在体内用几种不同的金属物质进行放射性标记。苊醌双的更大动力学稳定性相对于相应的脂肪族ATSM络合物，（氨基硫脲基）金属络合物允许许多成像探针的稳定化，特别关注用于PET应用的冷和热Cu（II）和Ga（III）衍生物以及用于SPECT的In-111（III）衍生物（单光子发射计算机断层扫描）应用，而Zn（II）衍生物在细胞中显示光学成像性质，相对于游离配体具有增强的荧光发射和寿命。初步研究表明，镓基苊醌双（氨基硫脲）配合物在体外也具有缺氧选择性，从而增加了人们对它们作为新一代成像剂在体外和体内应用的兴趣。
The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using (64)CuATSM [copper (diacetyl-bis(N4-methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21(st) century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in cold and hot Cu(II) and Ga(III) derivatives for PET applications and In-111(III) derivatives for SPECT (single-photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium-based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications.