Comprehensive Cancer Imaging Centre, Department of Cancer & Surgery, Faculty of Medicine, Imperial College London, Hammersmith Hospital, 240 MRC Cyclotron Building, Du Cane Road, London, W12 0NN, UK.
Mol Imaging Biol. 2012 Dec;14(6):753-61. doi: 10.1007/s11307-012-0554-2.
We evaluated whether 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) could be used as imaging biomarkers of platinum resensitization in ovarian cancer.
Paired platinum-sensitive and platinum-resistant ovarian cancer cells from the same patient, PEO1 and PEO4, grown as tumor xenografts in nude mice, were assessed by PET.
The AKT inhibitor, API-2, resensitized platinum-resistant PEO4 tumors to cisplatin, leading to a markedly lower Ki67 labeling index (p ≤ 0.006, n = 6 per group). [(18)F]FDG-PET and [(18)F]FLT-PET imaging variables were lower after combination treatment compared with vehicle treatment (p ≤ 0.006, n = 6 per group). No changes were seen with either drug alone. PRAS40 phosphorylation status was a sensitive biochemical marker of pathway inhibition, whereas reductions thymidine kinase 1 expression defined the [(18)F]FLT response.
Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [(18)F]FDG-PET and [(18)F]FLT-PET warranting further assessment.
我们评估了 2-脱氧-2-[(18)F]氟代-D-葡萄糖([(18)F]FDG)和 3'-脱氧-3'-[(18)F]氟代胸苷([(18)F]FLT)正电子发射断层扫描(PET)是否可作为卵巢癌铂类再敏化的成像生物标志物。
对来自同一患者的配对铂类敏感和铂类耐药卵巢癌细胞 PEO1 和 PEO4 进行评估，这些细胞在裸鼠中生长为肿瘤异种移植物，并进行 PET 检查。
AKT 抑制剂 API-2 使铂类耐药的 PEO4 肿瘤对顺铂重新敏感，导致 Ki67 标记指数明显降低(p ≤ 0.006，每组 6 只)。与载体治疗相比，联合治疗后 [(18)F]FDG-PET 和 [(18)F]FLT-PET 成像变量降低(p ≤ 0.006，每组 6 只)。单独使用任何一种药物都没有变化。PRAS40 磷酸化状态是通路抑制的敏感生化标志物，而胸苷激酶 1 表达的降低定义了 [(18)F]FLT 的反应。
获得性铂类耐药疾病中 AKT 激活的治疗性抑制可通过 [(18)F]FDG-PET 和 [(18)F]FLT-PET 进行无创成像，值得进一步评估。
