Yin Jipeng, Xin Bo, Zhang Mingru, Hui Xiaoli, Chai Na, Hu Hao, Xu Bing, Wang Jing, Nie Yongzhan, Zhou Guangqing, Wang Guanliang, Lu Hongbing, Yao Liping, Chen Liusheng, Wu Kaichun
School of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
Clinical Medical Research Center, The 75th Group Army Hospital of Chinese People's Liberation Army (PLA), Dali, China.
Front Oncol. 2021 Sep 30;11:750376. doi: 10.3389/fonc.2021.750376. eCollection 2021.
To synthesize the dimer of GX1 and identify whether its affinity and targeting are better than those of GX1. To prepare Ga-DOTA-KEK-(GX1) and to apply it to PET and Cerenkov imaging of gastric cancer.
Ga-DOTA-KEK-(GX1) was prepared, and the labeling yield and stability were determined. Its specificity and affinity were verified using an cell binding assay and competitive inhibition test, cell immunofluorescence, and cell uptake and efflux study. Its tumor-targeting ability was determined by nano PET/CT and Cerenkov imaging, standardized uptake value (SUV), signal-to-background ratio (SBR) quantification, and a biodistribution study in tumor-bearing nude mice.
Ga-DOTA-KEK-(GX1) was successfully prepared, and the labeling yield was more than 97%. It existed stably for 90 min in serum. The binding of Ga-DOTA-KEK-(GX1) to cocultured HUVECs (Co-HUVECs) was higher than that to human umbilical vein endothelial cells (HUVECs), BGC823 cells, and GES cells. It was also higher than that of Ga-DOTA-GX1, indicating that the dimer did improve the specificity and affinity of GX1. The binding of KEK-(GX1) to Co-HUVECs was significantly higher than that of GX1. Additionally, the uptake of Ga-DOTA-KEK-(GX1) by Co-HUVECs was higher than that of Ga-DOTA-GX1 and reached a maximum at 60 min. Nano PET/CT and Cerenkov imaging showed that the tumor imaging of the nude mice injected with Ga-DOTA-KEK-(GX1) was clear, and the SUV and SBR value of the tumor sites were significantly higher than those of the nude mice injected with Ga-DOTA-GX1, indicating that the probe had better targeting . Finally, the biodistribution showed quantitatively that when organs such as the kidney and liver metabolized rapidly, the radioactivity of the tumor site of the nude mice injected with Ga-DOTA-KEK-(GX1) decreased relatively slowly. At the same time, the percentage of injected dose per gram (%ID/g) of the tumor site was higher than that of other normal organs except the liver and kidney at 60 min, which indicated that the tumor had good absorption of the probe.
GX1 was modified successfully, and the and properties of the GX1 dimer were significantly better than those of GX1. The imaging probe, Ga-DOTA-KEK-(GX1), was successfully prepared, which provides a candidate probe for PET and Cerenkov diagnosis of gastric cancer.
合成GX1二聚体，鉴定其亲和力和靶向性是否优于GX1。制备Ga-DOTA-KEK-(GX1)并将其应用于胃癌的PET和切伦科夫成像。
制备Ga-DOTA-KEK-(GX1)，测定其标记率和稳定性。通过细胞结合试验、竞争抑制试验、细胞免疫荧光以及细胞摄取和流出研究验证其特异性和亲和力。通过纳米PET/CT和切伦科夫成像、标准化摄取值（SUV）、信号本底比（SBR）定量以及荷瘤裸鼠的生物分布研究确定其肿瘤靶向能力。
成功制备了Ga-DOTA-KEK-(GX1)，标记率超过97%。其在血清中稳定存在90分钟。Ga-DOTA-KEK-(GX1)与共培养的人脐静脉内皮细胞（Co-HUVECs）的结合高于与人脐静脉内皮细胞（HUVECs）、BGC823细胞和GES细胞的结合。它也高于Ga-DOTA-GX1，表明二聚体确实提高了GX1的特异性和亲和力。KEK-(GX1)与Co-HUVECs的结合明显高于GX1。此外，Co-HUVECs对Ga-DOTA-KEK-(GX1)的摄取高于Ga-DOTA-GX1，并在60分钟时达到最大值。纳米PET/CT和切伦科夫成像显示，注射Ga-DOTA-KEK-(GX1)的裸鼠肿瘤成像清晰，肿瘤部位的SUV和SBR值明显高于注射Ga-DOTA-GX1的裸鼠，表明该探针具有更好的靶向性。最后，生物分布定量显示，当肾脏和肝脏等器官快速代谢时，注射Ga-DOTA-KEK-(GX1)的裸鼠肿瘤部位的放射性下降相对较慢。同时，在60分钟时，肿瘤部位每克注射剂量百分比（%ID/g）高于除肝脏和肾脏外的其他正常器官，这表明肿瘤对该探针具有良好的摄取。
成功修饰了GX1，GX1二聚体的亲和力和靶向性明显优于GX1。成功制备了成像探针Ga-DOTA-KEK-(GX1)，为胃癌的PET和切伦科夫诊断提供了一种候选探针。
