Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging.
Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging.
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生物素和四嗪缀合物的酶促氟化用于正电子发射断层扫描成像的预靶向方法。
DOI：
10.1002/cbic.201800234
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Lowe PT
中科院分区：
文献类型：
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作者：
Lowe PT
放射性标记的抗体和抗体衍生的重组构建体的使用已显示出用于成像和治疗用途的前景。在这种情况下，生物素-抗生物素蛋白/链霉抗生物素蛋白配对，沿着逆电子需求狄尔斯-阿尔德（iEDDA）反应，已在正电子发射断层扫描（PET）的预靶向方法中得到应用。本研究报告了两种抗体预靶向工具（FDA-PEG-四嗪和[18 F]FDA-PEG-生物素）的氟酶介导的转卤化[5′-氯-5 ′-脱氧腺苷（ClDA）底物转化为5′-氟-5 ′-脱氧腺苷（FDA）产物]，并评估了每种工具对iEDDA连接反式环辛烯的相容性或对抗生物素蛋白的亲和力。开发了一种方案，以避免在[18 F] FDA-PEG-生物素合成过程中生物素的放射性促进氧化。该研究增加了用于PET的氟化酶催化放射合成的缀合物的库，并表明氟化酶将接受在腺嘌呤环的C-2处与PEG化货物连接的广泛的ClDA底物。该方法是例外的，因为与[18F]氟化物的亲核反应在中性pH和环境温度下在水中发生。
The use of radiolabelled antibodies and antibody‐derived recombinant constructs has shown promise for both imaging and therapeutic use. In this context, the biotin–avidin/streptavidin pairing, along with the inverse‐electron‐demand Diels–Alder (iEDDA) reaction, have found application in pretargeting approaches for positron emission tomography (PET). This study reports the fluorinase‐mediated transhalogenation [5′‐chloro‐5′‐deoxyadenosine (ClDA) substrates to 5′‐fluoro‐5′‐deoxyadenosine (FDA) products] of two antibody pretargeting tools, a FDA‐PEG‐tetrazine and a [18F]FDA‐PEG‐biotin, and each is assessed either for its compatibility towards iEDDA ligation totrans‐cyclooctene or for its affinity to avidin. A protocol to avoid radiolytically promoted oxidation of biotin during the synthesis of [18F]FDA‐PEG‐biotin was developed. The study adds to the repertoire of conjugates for use in fluorinase‐catalysed radiosynthesis for PET and shows that the fluorinase will accept a wide range of ClDA substrates tethered at C‐2 of the adenine ring with a PEGylated cargo. The method is exceptional because the nucleophilic reaction with [18F]fluoride takes place in water at neutral pH and at ambient temperature.