The Massachusetts General Hospital Radiochemistry Program, in collaboration with Pfizer, has developed unique 11C and 18F-labeling strategies to synthesize isotopologs of lorlatinib (PF-06463922) which is undergoing phase III clinical trial investigations for treatment of non-small-cell lung cancers with specific molecular alterations. A major goal in cancer therapeutics is to measure the concentrations of this drug in the brain metastases of patients with lung cancer, and penetration of the blood-brain barrier is important for optimal therapeutic outcomes. Our recent publication in Nature Communications employed radiolabeled lorlatinib and positron emission tomography (PET) studies in preclinical models including nonhuman primates (NHPs) that demonstrated high brain permeability of this compound. Our future work with radiolabeled lorlatinib will include advanced PET evaluations in rodent tumor models and normal NHPs with the goal of clinical translation.

中文翻译：

---

PET证实了ROS1 / ALK抑制剂Lorlatinib的脑渗透。

麻省总医院放射化学计划与辉瑞公司合作，开发了独特的11C和18F标记策略来合成lorlatinib（PF-06463922）的同系物，该药物正在接受III期临床试验研究，以治疗非小细胞肺癌。具体的分子变化。癌症治疗的主要目标是测量肺癌患者脑转移中该药物的浓度，血脑屏障的渗透对于最佳治疗效果非常重要。我们最近在《自然通讯》上发表的论文在包括非人类灵长类动物（NHP）在内的临床前模型中采用了放射性标记的lorlatinib和正电子发射断层扫描（PET）研究，证明该化合物具有很高的脑通透性。