Ye Qianni, Liu Zhenfeng, Zhang Shuyi, Wang Guolin, Wen Guanghua, Dong Mengjie
Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Cancers (Basel). 2023 Jan 26;15(3):755. doi: 10.3390/cancers15030755.
N-cadherin is considered a characteristic protein of EMT and has been found to be closely related to tumor resistance. In this study, a novel molecular imaging probe, Tc-HYNIC-ADH-1, was developed, and its diagnostic value in monitoring drug resistance in NSCLC was preliminarily investigated.
ADH-1 was labeled indirectly with Tc. Radiochemical purity and stability, partition coefficients and pharmacokinetics were evaluated. Additionally, the fluorescent probe of ADH-1 was synthesized to study tumor uptake in cells level and in vivo. Biodistribution analysis and small animal SPECT/CT were performed in PC9GR and PC9 tumor-bearing mice.
Tc-HYNIC-ADH-1 was highly stable (radiochemical purity ≥ 98% in PBS and serum after 24 h). A cell binding study and fluorescence imaging showed that the uptake was significantly higher in PC9GR cells (gefitinib-resistant) than in PC9 cells (nonresistant) ( < 0.05). Biodistribution analysis showed rapid blood clearance and significant uptake in the kidney and resistant tumor. Small animal SPECT/CT studies showed that uptake in PC9GR tumors (T/NT = 7.73 ± 0.54) was significantly higher than that in PC9 tumors (T/NT = 3.66 ± 0.78) at 1 h ( = 0.002).
The Tc-HYNIC-ADH-1 molecular probe has a short synthesis time, high labeling rate, high radiochemical purity and good stability, does not require purification, is characterized by rapid blood clearance and is mainly excreted through the urinary system. Tc-HYNIC-ADH-1 is considered a promising probe for monitoring drug resistance in NSCLC.
N-钙黏蛋白被认为是上皮-间质转化的特征性蛋白，且已发现其与肿瘤耐药性密切相关。在本研究中，开发了一种新型分子成像探针Tc-HYNIC-ADH-1，并初步研究了其在监测非小细胞肺癌耐药性方面的诊断价值。
用Tc间接标记ADH-1。评估放射化学纯度和稳定性、分配系数及药代动力学。此外，合成ADH-1的荧光探针以研究细胞水平和体内的肿瘤摄取情况。对PC9GR和荷PC9肿瘤小鼠进行生物分布分析和小动物SPECT/CT检查。
Tc-HYNIC-ADH-1高度稳定（24小时后在PBS和血清中的放射化学纯度≥98%）。细胞结合研究和荧光成像显示，PC9GR细胞（吉非替尼耐药）中的摄取明显高于PC9细胞（非耐药）（<0.05）。生物分布分析显示血液清除迅速，在肾脏和耐药肿瘤中有明显摄取。小动物SPECT/CT研究显示，1小时时PC9GR肿瘤的摄取（T/NT = 7.73±0.54）明显高于PC9肿瘤（T/NT = 3.66±0.78）（=0.002）。
Tc-HYNIC-ADH-1分子探针合成时间短、标记率高、放射化学纯度高且稳定性好，无需纯化，具有血液清除迅速的特点，主要通过泌尿系统排泄。Tc-HYNIC-ADH-1被认为是监测非小细胞肺癌耐药性的一种有前景的探针。
