Because of our interest in developing new hybrid peptide radioconjugates with suitable biochemical properties for multiple-receptors targeting properties that are overexpressed on many human cancers especially ovarian cancer, we have synthesized ⁶⁸Ga-NODAGA-MUC1 and ⁶⁸Ga-NODAGA-MUC1-FA hybrid peptide conjugates using a straightforward and one-step simple reaction. Radiochemical yields were found to be higher than 95% (decay corrected), with a total synthesis time of less than 20 min. Radiochemical purities were always higher than 95% without HPLC purification. In vitro studies on KB cancer cells showed that substantial amounts of the radioconjugates were associated with cell fractions and held great affinities and specificities toward the KB cell line. In vivo characterization in normal female Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary system. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for ⁶⁸Ga-NODAGA-MUC1-FA hybrid peptide conjugate compared to the ⁶⁸Ga-NODAGA-MUC1 peptide monomeric counterpart. The uptake in the tumors was blocked by the excess injection of hybrid peptide, suggesting a receptor-mediated process. These results demonstrate that ⁶⁸Ga-NODAGA-MUC1-FA hybrid peptide conjugate may be useful as a molecular probe for early detection and staging of folate and MUC1 receptor-positive cancers such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment.

中文翻译：

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用于诊断卵巢癌的 68Ga-Mucin1 及其叶酸杂化肽缀合物的合成、放射性标记和生物学评价

由于我们有兴趣开发具有合适生化特性的新型杂化肽放射性偶联物，以针对在许多人类癌症特别是卵巢癌中过度表达的多受体靶向特性，我们合成了⁶⁸ Ga-NODAGA-MUC1 和⁶⁸ Ga-NODAGA-MUC1-FA 杂合体肽偶联物使用直接且一步简单的反应。发现放射化学产率高于 95%（衰减校正），总合成时间少于 20 分钟。未经 HPLC 纯化，放射化学纯度始终高于 95%。对 KB 癌细胞的体外研究表明，大量的放射性缀合物与细胞组分相关，并且对 KB 细胞系具有很高的亲和力和特异性。正常雌性 Balb/c 小鼠的体内表征显示这些放射性偶联物的血液快速清除，主要通过泌尿系统排泄。在携带人 KB 细胞系异种移植物的裸鼠中的生物分布研究表明，与⁶⁸ Ga-NODAGA-MUC1 肽单体对应物相比，⁶⁸ Ga-NODAGA-MUC1-FA 杂合肽缀合物具有显着的肿瘤吸收和有利的生物分布特征。肿瘤中的摄取被混合肽的过量注射阻断，表明受体介导的过程。这些结果表明⁶⁸Ga-NODAGA-MUC1-FA 杂合肽缀合物可用作分子探针，用于叶酸和 MUC1 受体阳性癌症（如卵巢癌及其转移）的早期检测和分期，以及监测肿瘤对治疗的反应。