Department of Medical Imaging and Nuclear Medicine, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Surgical Oncology and Hepatobiliary Surgery, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
PLoS One. 2018 Jun 12;13(6):e0199024. doi: 10.1371/journal.pone.0199024. eCollection 2018.
c-Met is a receptor tyrosine kinase shown inappropriate expression and actively involved in progression and metastasis in most types of human cancer. Development of c-Met-targeted imaging and therapeutic agents would be extremely useful. Previous studies reported that c-Met-binding peptide (Met-pep1, YLFSVHWPPLKA) specifically targets c-Met receptor. Here, we evaluated 18F-labeled Met-pep1 for PET imaging of c-Met positive tumor in human head and neck squamous cell carcinoma (HNSCC) xenografted mice.
c-Met-binding peptide, Met-pep1, was synthesized and labeled with 4-nitrophenyl [18F]-2-fluoropropionate ([18F]-NPFP) ([18F]FP-Met-pep1). The cell uptake, internalization and efflux of [18F]FP-Met-pep1 were assessed in UM-SCC-22B cells. In vivo pharmacokinetics, blocking and biodistribution of the radiotracers were investigated in tumor-bearing nude mice by microPET imaging.
The radiolabeling yield for [18F]FP-Met-pep1 was over 55% with 97% purity. [18F]FP-Met-pep1 showed high tumor uptake in UM-SCC-22B tumor-bearing mice with clear visualization. The specificity of the imaging tracer was confirmed by significantly decreased tumor uptake after co-administration of unlabeled Met-pep1 peptides. Prominent uptake and rapid excretion of [18F]FP-Met-pep1 was also observed in the kidney, suggesting this tracer is mainly excreted through the renal-urinary routes. Ex vivo biodistribution showed similar results that were consistent with microPET imaging data.
These results suggest that 18F-labeled c-Met peptide may potentially be used for imaging c-Met positive HNSCC cancer in vivo and for c-Met-targeted cancer therapy.
c-Met 是一种受体酪氨酸激酶，在大多数类型的人类癌症中表现出异常表达，并积极参与肿瘤的进展和转移。开发 c-Met 靶向成像和治疗剂将是非常有用的。先前的研究报告称，c-Met 结合肽（Met-pep1，YLFSVHWPPLKA）特异性靶向 c-Met 受体。在这里，我们评估了 18F 标记的 Met-pep1 用于人头颈鳞状细胞癌（HNSCC）异种移植小鼠中 c-Met 阳性肿瘤的 PET 成像。
合成了 c-Met 结合肽 Met-pep1，并与 4-硝基苯[18F]-2-氟丙酸酯（[18F]-NPFP）[18F]FP-Met-pep1 标记。在 UM-SCC-22B 细胞中评估了[18F]FP-Met-pep1 的细胞摄取、内化和外排。通过 microPET 成像研究了放射性示踪剂在荷瘤裸鼠中的体内药代动力学、阻断和生物分布。
[18F]FP-Met-pep1 的放射性标记产率超过 55%，纯度为 97%。[18F]FP-Met-pep1 在荷 UM-SCC-22B 肿瘤的小鼠中表现出高肿瘤摄取，可清晰显影。在用未标记的 Met-pep1 肽共同给药后，肿瘤摄取明显减少，证实了成像示踪剂的特异性。[18F]FP-Met-pep1 在肾脏中也表现出明显的摄取和快速排泄，表明该示踪剂主要通过肾脏-尿液途径排泄。离体生物分布显示出与 microPET 成像数据一致的相似结果。
这些结果表明，18F 标记的 c-Met 肽可能有潜力用于体内成像 c-Met 阳性 HNSCC 癌症，并用于 c-Met 靶向癌症治疗。
