Abstract
Rationale: Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of c-Met signaling pathway contributes to tumorigenesis and cancer progression, and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for treating NSCLC, and the methods for noninvasive in vivo assessment of c-Met expression will improve NSCLC treatment and diagnosis. Methods: A new peptide-based (cMBP) radiotracer targeting c-Met, 99mTc-hydrazine nicotinamide (HYNIC)-cMBP, was developed for single photon emission computed tomography (SPECT) imaging. Cell uptake assays were performed on two NSCLC cell lines with different c-Met expression: H1993 (high expression) and H1299 (no expression). In vivo tumor specificity was assessed by SPECT imaging in tumor-bearing mice at 0.5, 1, 2 and 4 h after injection of the probe. Blocking assays, biodistribution and autoradiography were also conducted to determine probe specificity. Results: 99mTc-HYNIC-cMBP was prepared with high efficiency and showed higher uptake in H1993 cells than H1299 cells. Biodistribution and autoradiography also showed significantly higher accumulation of 99mTc-HYNIC-cMBP in H1993 tumors than H1299 (H1993: 4.74±1.43 %ID/g and H1299: 1.00±0.37 %ID/g at 0.5h, p<0.05). H1993 tumors were clearly visualized at 0.5h in SPECT images, whereas H1299 tumors were not observed at any time. Specificity of 99mTc-HYNIC-cMBP to c-Met was demonstrated by competitive block with excess un-radiolabeled peptide. Conclusion: We developed a novel SPECT tracer, 99mTc-HYNIC-cMBP, for c-Met-targeted imaging in NSCLC that specifically bound to c-Met with favorable pharmacokinetics in vitro and in vivo.
- Animal Imaging
- Molecular Imaging
- Oncology: Lung
- SPECT
- c-Met
- non-small cell lung cancer (NSCLC)
- targeted peptide
- Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.