Metran-Nascente Cristiane, Yeung Ivan, Vines Douglass C, Metser Ur, Dhani Neesha C, Green David, Milosevic Michael, Jaffray David, Hedley David W
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and.
J Nucl Med. 2016 Mar;57(3):361-6. doi: 10.2967/jnumed.115.167650. Epub 2016 Jan 14.
Pancreatic cancers are thought to be unusually hypoxic, which might sensitize them to drugs that are activated under hypoxic conditions. In order to develop this idea in the clinic, a minimally invasive technique for measuring the oxygenation status of pancreatic cancers is needed.
We tested the potential for minimally invasive imaging of hypoxia in pancreatic cancer patients, using the 2-nitroimidazole PET tracer (18)F-fluoroazomycin arabinoside (or (18)F-1-α-D-[5-fluoro-5-deoxyarabinofuranosyl]-2-nitroimidazole [(18)F-FAZA]). Dynamic and static scans were obtained in 21 patients with either locally advanced or metastatic disease. The hypoxic fraction was determined in the 2-h static scans as the percentage of voxels with SUVs more than 3 SDs from the mean values obtained for skeletal muscle.
Hypoxia was detected in 15 of 20 evaluable patients, with the hypoxic fraction ranging from less than 5% to greater than 50%. Compartmental analysis of the dynamic scans allowed us to approximate the tumor perfusion as mL/min/g of tissue, a value that is independent of the extent of hypoxia derived from tracer uptake in the 2-h static scan. There was no significant correlation between tumor perfusion and hypoxia; nor did we see an association between tumor volume and hypoxia.
Although pancreatic cancers can be highly hypoxic, a substantial proportion appears to be well oxygenated. Therefore, we suggest that a minimally invasive technique such as the one described in this study be used for patient stratification in future clinical trials of hypoxia-targeting agents.
胰腺癌被认为存在异常缺氧情况，这可能使它们对在缺氧条件下被激活的药物敏感。为了在临床上验证这一观点，需要一种用于测量胰腺癌氧合状态的微创技术。
我们使用2-硝基咪唑PET示踪剂（18）F-氟阿糖胞苷（或（18）F-1-α-D-[5-氟-5-脱氧阿拉伯呋喃糖基]-2-硝基咪唑[（18）F-FAZA]），测试了对胰腺癌患者进行缺氧微创成像的潜力。对21例局部晚期或转移性疾病患者进行了动态和静态扫描。在2小时静态扫描中，将缺氧分数确定为SUV值比骨骼肌平均值高出3个标准差以上的体素百分比。
在20例可评估患者中，有15例检测到缺氧，缺氧分数范围从小于5%到大于50%。对动态扫描进行的房室分析使我们能够将肿瘤灌注近似为每克组织毫升/分钟，该值与2小时静态扫描中示踪剂摄取所产生的缺氧程度无关。肿瘤灌注与缺氧之间无显著相关性；我们也未发现肿瘤体积与缺氧之间存在关联。
尽管胰腺癌可能高度缺氧，但相当一部分似乎氧合良好。因此，我们建议在未来针对缺氧靶向药物的临床试验中，使用本研究中描述的微创技术对患者进行分层。
