背景:N-cadherin被认为是EMT的特征性蛋白,已发现与肿瘤耐药密切相关。在这项研究中,一种新型分子成像探针,99mTc-HYNIC-ADH-1,被开发,并初步探讨其在非小细胞肺癌耐药监测中的诊断价值。
方法:ADH-1间接标记99mTc。放射化学纯度和稳定性,评价了分配系数和药代动力学。此外,合成了ADH-1荧光探针,以研究细胞水平和体内肿瘤的摄取。在PC9GR和PC9荷瘤小鼠中进行生物分布分析和小动物SPECT/CT。
结果:99mTc-HYNIC-ADH-1高度稳定(24小时后在PBS和血清中放射化学纯度≥98%)。细胞结合研究和荧光成像显示PC9GR细胞(吉非替尼耐药)的摄取明显高于PC9细胞(非耐药)(p<0.05)。生物分布分析显示,肾脏和耐药肿瘤的血液清除速度快,吸收明显。小动物SPECT/CT研究表明,PC9GR肿瘤(T/NT=7.73±0.54)在1小时(p=0.002)的摄取显着高于PC9肿瘤(T/NT=3.66±0.78)。
结论:99mTc-HYNIC-ADH-1分子探针合成时间短,贴标率高,放射化学纯度高,稳定性好,不需要净化,以快速的血液清除为特征,主要通过泌尿系统排泄。99mTc-HYNIC-ADH-1被认为是监测NSCLC耐药性的有希望的探针。
BACKGROUND: 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, 99mTc-HYNIC-ADH-1, was developed, and its diagnostic value in monitoring drug resistance in NSCLC was preliminarily investigated.
METHODS: ADH-1 was labeled indirectly with 99mTc. 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.
RESULTS: 99mTc-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) (p < 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 (p = 0.002).
CONCLUSIONS: The 99mTc-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. 99mTc-HYNIC-ADH-1 is considered a promising probe for monitoring drug resistance in NSCLC.