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J Nucl Med. 2018 Nov;59(11):1686-1691. doi: 10.2967/jnumed.117.206730. Epub 2018 May 18.

Development of a SPECT Tracer to Image c-Met Expression in a Xenograft Model of Non-Small Cell Lung Cancer.

Han Z1,2, Xiao Y1,2, Wang K1,2, Yan J1,2, Xiao Z1,2, Fang F1,2, Jin Z1,2, Liu Y1,2, Sun X1,2,3, Shen B4,2.

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Molecular Imaging Research Center, Harbin Medical University, Harbin, Heilongjiang, China.
TOF-PET/CT/MR Center, Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China; and.
Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, California.
Molecular Imaging Research Center, Harbin Medical University, Harbin, Heilongjiang, China


Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of the 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 NSCLC, and methods for noninvasive in vivo assessment of c-Met expression would improve NSCLC treatment and diagnosis. Methods: We developed a new c-Met-binding peptide (cMBP) radiotracer, 99mTc-hydrazine nicotinamide (HYNIC)-cMBP, for SPECT imaging. Cell uptake assays were performed on 2 NSCLC cell lines with different c-Met expressions: 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 in H1299 cells. Biodistribution and autoradiography also showed significantly higher percentages of the injected dose for 99mTc-HYNIC-cMBP in H1993 tumors than in H1299 tumors at 0.5 h (4.74 ± 1.43%/g and 1.00 ± 0.37%/g, respectively; P < 0.05). H1993 tumors were clearly visualized at 0.5 h in SPECT images, whereas H1299 tumors were not observed at any time. The specificity of 99mTc-HYNIC-cMBP for c-Met was demonstrated by a competitive block with an excess of nonradiolabeled peptide. Conclusion: For c-Met-targeted SPECT imaging of NSCLC, we developed 99mTc-HYNIC-cMBP, a tracer that specifically binds to c-Met with favorable pharmacokinetics in vitro and in vivo.


NSCLC; SPECT; c-Met; targeted peptide


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