Abstract
1099
Objectives: Targeted drug therapy using epidermal growth factor (EGFR) tyrosine kinase inhibitor (TKI) improves the survival rate and quality of life for patients with NSCLC. c-Met is closely correlated with the invasion and metastasis of lung cancer as well as the drug resistance to EGFR-TKI. c-Met inhibitor can benefit the survival of patients with NSCLC. In the present study, a novel 99Tcm-tricine-EDDA-Hynic-c-Metmolecular probe was synthetized, and nude mice models of human non-small-cell lung cancer were established in order to preliminarily investigate that whether the molecular probe can be used in NSCLC imaging to screen c-Met inhibitor for targeted drug therapy in NSCLC.
Methods: With Hynic as the chelating agent, 99mTcO4-labeled c-Met receptor was used to synthetize a novel 99Tcm-tricine-EDDA-Hynic-c-Met. Human non-small-cell lung cancer cell line H1993 and human lung cancer lymph node metastasis cell line H292 were inoculated subcutaneously in the right shoulder in three nude mice, respectively, so as to establish nude mice models. After the duration of 4-6 weeks when the diameter of tumors was about 1.0-1.5cm, experiment of in vivo distribution and imaging were performed. Two nude mice successfully transplanted with H1993 tumor and two nude transplanted with H292 tumor were injected with 99Tcm-tricine-EDDA-Hynic-c-Met through the tail vein. After 2h and 4h, micro-SPECT/CT imaging was performed.
Results: The labeling efficiency of99Tcm-tricine-EDDA-Hynic-c-Met was 90.8%±5.0%, and radiochemicalpurity was over 95%. There was statistical significance incombination rate between H1993 cell line and H292 cell line with 99Tcm-tricine-EDDA-Hynic-c-Met at 45min (2.65% ± 0.41% vs 1.53% ± 0.21%; t = 4.579, P = 0.0102), 2h (2.13% ± 0.21% and 0.96% ± 0.39%; t = 4.594, P = 0.0101) and 4h (3.11% ± 0.16% vs 0.74% ± 1.08%; t = 3.763, P = 0.0197). Differences of combination rate of H1993 cell line with 99Tcm-tricine-EDDA-Hynic-c-Met were statistically significant at 2h and 4h (t = 6.340, P = 0.0032). Micro-SPECT/CT imaging of nude mice transplanted with H1993 and H292 tumors using99Tcm-tricine-EDDA-Hynic-c-Met showed that uptake of 99Tcm-tricine-EDDA-Hynic-c-Met was high in H1993 tumor, while it was mild in H292 tumor both at the time points of 2h and 4h(Figure 1). Semi-quantitative analysis of the ratio of radioactivity intensity at tumor site to radioactivity intensity of adjacent muscles (T/N value) showed that the average T/N value of the uptake of 99Tcm-tricine-EDDA-Hynic-c-Metin H1993 and H292 tumors at 2h was 3.90 and 2.85, respectively,while it was 4.88 and 2.36 at 4h.
Conclusions: Using c-Met as the target, SPECT/CT imaging through radioactive isotopes labeled 99Tcm-tricine-EDDA-Hynic-c-Met molecular probe can be used to screen indicators of NSCLC treated by c-Met inhibitor-mediated targeted drug therapy, which provides idea for further research.