Development of ^99mTc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental...

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.

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.

^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).

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.