Department of Oncology, Karmanos Cancer Institute, 4100 John R. Street, Detroit, MI, 48201, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Sci Rep. 2018 Jun 13;8(1):9043. doi: 10.1038/s41598-018-27454-6.
Tumor resistance to treatment paved the way toward the development of single agent drugs that target multiple molecular signatures amplified within the malignancy. The discovered crosstalk between EGFR and HER3 as well as the role of HER3 in mediating EGFR resistance made these two receptor tyrosine kinases attractive targets. MEHD7945A or duligotuzumab is a single immunotherapy agent that dually targets both molecular signatures. In this study, a positron emission tomography (PET) companion diagnostic to MEHD7945A is reported and evaluated in pancreatic cancer. Tumor accretion and whole body pharmacokinetics of Zr-MEHD7945A were established. Specificity of the probe for EGFR and/or HER3 was further examined.
肿瘤对治疗的耐药性为开发针对恶性肿瘤中扩增的多种分子特征的单一药物铺平了道路。已经发现 EGFR 和 HER3 之间的串扰以及 HER3 在介导 EGFR 耐药中的作用，使得这两个受体酪氨酸激酶成为有吸引力的靶标。MEHD7945A 或 duligotuzumab 是一种双重靶向这两种分子特征的单一免疫治疗药物。本研究报告并评估了一种用于 MEHD7945A 的正电子发射断层扫描 (PET) 伴随诊断剂在胰腺癌中的应用。建立了 Zr-MEHD7945A 的肿瘤积累和全身药代动力学。进一步研究了探针对 EGFR 和/或 HER3 的特异性。
