基于肽的 68Ga-PET 放射性示踪剂用于成像结直肠癌中 CD133 的表达。
Peptide-based 68Ga-PET radiotracer for imaging CD133 expression in colorectal cancer.
机构信息
Departments of Radiology.
Nuclear Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Auhui, China.
出版信息
Nucl Med Commun. 2021 Oct 1;42(10):1144-1150. doi: 10.1097/MNM.0000000000001435.
OBJECTIVE
CD133 is a demonstrated cancer stem cell marker. A small peptide LS7, screened by a phage display technique, was identified to specifically target CD133. The purpose of this study was to develop a novel and specific peptide-based PET imaging agent for CD133 imaging in colorectal cancer.
METHODS
The peptide LS7 was conjugated with 1,4,7,20-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with 68Ga. The cellular uptake was assessed in vitro. In vivo small-animal PET/CT and ex vivo biodistribution evaluations were performed in mice bearing CD133-positive HCT116 and Lovo cell-derived tumors as well as CD133-negative DLD1 cell-derived tumors. Nonspecific uptake of the tracer in HCT116 cell-derived tumor cells and tumor models was determined by coincubation or coinjection with an excess of unlabeled DOTA-LS7 along with radiolabeled tracers.
RESULTS
68Ga-DOTA-LS7 was produced with 80.0% yield and the radiochemical purity was greater than 95.0%. In vitro, 68Ga-DOTA-LS7 was selectively taken up by HCT116 and Lovo cells but not by DLD1 cells. Small-animal PET/CT clearly revealed deposition of 68Ga-DOTA-LS7 in HCT116 and Lovo cell-derived tumors with excellent contrast. Biodistribution demonstrated that the tumor uptakes were 2.24 ± 0.16, 1.76 ± 0.42, and 0.69 ± 0.28% ID/g in HCT116, Lovo and DLD1 cell-derived tumors, respectively, at 90 min post-injection. Uptake of 68Ga-DOTA-LS7 in HCT116 tumors was significantly inhibited by coinjection of excess DOTA-LS7.
CONCLUSION
Rapid tumor CD133 detection and selectivity were demonstrated in vitro and in vivo with PET using the specific CD133 binding peptide 68Ga-DOTA-LS7. A robust correlation was detected in vivo between tumor signals from mouse xenograft models with different cell lines and CD133 expression. The favorable characteristics of 68Ga-DOTA-LS7, such as convenient synthesis and specific uptake, warrant its further investigation for CD133 expression imaging.
目的
CD133 是一种已被证实的癌症干细胞标志物。一种通过噬菌体展示技术筛选出的小肽 LS7 被鉴定为可特异性靶向 CD133。本研究旨在开发一种新型、特异性的基于肽的 PET 成像剂，用于结直肠癌的 CD133 成像。
方法
将肽 LS7 与 1,4,7,20-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）缀合，并通过 68Ga 进行放射性标记。在体外评估细胞摄取率。在携带 CD133 阳性 HCT116 和 Lovo 细胞衍生肿瘤以及 CD133 阴性 DLD1 细胞衍生肿瘤的小鼠中进行小动物 PET/CT 和离体生物分布评估。通过与未标记的 DOTA-LS7 共孵育或共注射以及放射性示踪剂，确定示踪剂在 HCT116 细胞衍生肿瘤细胞和肿瘤模型中的非特异性摄取。
结果
68Ga-DOTA-LS7 的产率为 80.0%，放射化学纯度大于 95.0%。体外，68Ga-DOTA-LS7 被 HCT116 和 Lovo 细胞选择性摄取，但不被 DLD1 细胞摄取。小动物 PET/CT 清楚地显示了 68Ga-DOTA-LS7 在 HCT116 和 Lovo 细胞衍生肿瘤中的沉积，具有极好的对比度。生物分布显示，在注射后 90 分钟，HCT116、Lovo 和 DLD1 细胞衍生肿瘤中的肿瘤摄取率分别为 2.24±0.16%ID/g、1.76±0.42%ID/g 和 0.69±0.28%ID/g。68Ga-DOTA-LS7 在 HCT116 肿瘤中的摄取在共注射过量 DOTA-LS7 时显著受到抑制。
结论
使用特异性 CD133 结合肽 68Ga-DOTA-LS7，在体外和体内通过 PET 快速检测和选择性检测到肿瘤 CD133。在具有不同细胞系的小鼠异种移植模型中，体内肿瘤信号与 CD133 表达之间存在很强的相关性。68Ga-DOTA-LS7 的有利特性，如方便的合成和特异性摄取，使其进一步用于 CD133 表达成像研究。
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