The aim of this study was to prepare a novel 68Ga-labeled pH (low) insertion peptide (pHLIP)-like peptide, YJL-4, and determine its value for the early diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. The novel peptide YJL-4 was designed using a template-assisted method and synthesized by solid-phase peptide synthesis. After modification with the chelator 1,4,7‑triazacyclononane-N,N′,N″-triacetic acid (NOTA), the peptide was labeled with 68Ga. Then, the biodistribution of 68Ga-YJL-4 in tumor-bearing nude mice was investigated, and the mice were imaged by small animal positron emission tomography (PET). The radiochemical yield and radiochemical purity of 68Ga-YJL-4 were 89.5 ± 0.16% and 97.95 ± 0.06%, respectively. The biodistribution of 68Ga-YJL-4 in tumors (5.94 ± 1.27% ID/g, 6.72 ± 1.69% ID/g and 4.54 ± 0.58% ID/g at 1, 2 and 4 h after injection, respectively) was significantly greater than that of the control peptide in tumors at the corresponding time points (P < 0.01). Of the measured off-target organs, 68Ga-YJL-4 was highly distributed in the liver and blood. The small animal PET imaging results were consistent with the biodistribution results. The tumors were visualized by PET at 2 and 4 h after the injection of 68Ga-YJL-4. No tumors were observed in the control group. The novel pHLIP family peptide YJL-4 can adopt an α-helical structure for easy insertion into the cell membrane in an acidic environment. 68Ga-YJL-4 was produced in high radiochemical yield with good stability and can target TNBC tissue. Moreover, the strong concentration of radioactive 68Ga-YJL-4 in the abdomen does not hinder the imaging of early TNBC.

中文翻译：

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在三阴性乳腺癌小鼠模型中使用 68Ga 标记的 pH（低）插入肽样肽 YJL-4 进行小动物 PET 成像

本研究的目的是制备一种新型68Ga标记pH（低）插入肽（pHLIP）样肽YJL-4，并通过体内测定其对​​三阴性乳腺癌（TNBC）早期诊断的价值。荷瘤裸鼠的成像。采用模板辅助方法设计新型肽YJL-4，并通过固相肽合成法合成。用螯合剂 1,4,7-三氮杂环壬烷-N,N',N''-三乙酸 (NOTA) 修饰后，肽被标记为 68Ga。然后，研究了68Ga-YJL-4在荷瘤裸鼠体内的生物分布，并通过小动物正电子发射断层扫描（PET）对小鼠进行成像。 68Ga-YJL-4的放射化学收率和放射化学纯度分别为89.5±0.16%和97.95±0.06%。 68Ga-YJL-4 在肿瘤中的生物分布（注射后 1、2 和 4 小时分别为 5.94 ± 1.27% ID/g、6.72 ± 1.69% ID/g 和 4.54 ± 0.58% ID/g）显着大于对照肽在相应时间点肿瘤中的变化（P < 0.01）。在测量的脱靶器官中，68Ga-YJL-4高度分布在肝脏和血液中。小动物PET成像结果与生物分布结果一致。注射 68Ga-YJL-4 后 2 小时和 4 小时通过 PET 观察肿瘤。对照组未观察到肿瘤。新型pHLIP家族肽YJL-4可采用α-螺旋结构，在酸性环境下易于插入细胞膜。 68Ga-YJL-4 的放射化学产率高，稳定性好，可以靶向 TNBC 组织。而且，腹部高浓度的放射性68Ga-YJL-4并不妨碍早期TNBC的成像。