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

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Zhaoguo HanBaozhong Shen

Abstract

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 ...Continue Reading

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Citations

Jul 6, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Tim Van den WyngaertOra Israel
Jan 12, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Simon KlinglerJason P Holland
May 29, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yongjia TangYueqing Gu
Mar 21, 2020·Current Medicinal Chemistry·Rui CaoZhen Cheng
May 24, 2019·Bioconjugate Chemistry·Rachael FayJason P Holland

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