Development of a novel site-specific 18F protein labeling method and application for synthesis of 18F-EGF

我们制备了NODAGA-EGF作为分子探针，并在熊本大学建立了分子成像装置。采用Fmoc固相法合成了由53个氨基酸残基组成的表皮生长因子。肽链延长后，在N端引入了NODAGA(TBU)3。完全保护的多肽树脂在TFA溶液中处理，从树脂中解离并去除保护基团。高效液相色谱纯化后，形成二硫键，得到标记前驱体。接下来，为了进行分子成像研究，建立了SPECT/CT。我们建立了通过DOTA络合剂与Ga-67形成稳定络合物的方法。检查SPECT装置的定量准确性和图像分辨率。对荷小细胞肺癌细胞(H69)的小鼠进行了67Ga-DOTA-octreotate SPECT显像。结果，我们观察到Ga-67在H69肿瘤中的蓄积。

We prepared NODAGA-EGF as a molecular probe and set up the molecular imaging device in Kumamoto University. EGF, which consists of 53 amino acid residues, was synthesized by Fmoc solid-phase method. After elongation of peptide chain, NODAGA(tBu)3 was introduced at N-terminus. Fully protected peptide resin was treated in TFA solution to cleave from resin and remove protection groups. After HPLC purification, disulfide bonds were formed to give the labeling precursor. Next, to perform molecular imaging study, SPECT/CT was set up. We established a method to form stable complex with Ga-67 via DOTA chelator. SPECT device was checked the accuracy of quantification and image resolution. SPECT imaging using 67Ga-DOTA-octreotate was carried out on the mouse implanted with small cell lung tumor cell (H69). As the result, we could observe the accumulation of the Ga-67 in H69 tumor.