神秘的
酸中毒
Pet成像
医学
正电子发射断层摄影术
核医学
化学
病理
内科学
替代医学
作者
Gang Huang,Tian Zhao,Chensu Wang,Kien Nham,Yahong Xiong,Xiaofei Gao,Yihui Wang,Guiyang Hao,Woo‐Ping Ge,Xiankai Sun,Baran D. Sumer,Jinming Gao
标识
DOI:10.1038/s41551-019-0416-1
摘要
Owing to the diversity of cancer types and the spatiotemporal heterogeneity of tumour signals, high-resolution imaging of occult malignancy is challenging. 18F-fluorodeoxyglucose positron emission tomography allows for near-universal cancer detection, yet in many clinical scenarios it is hampered by false positives. Here, we report a method for the amplification of imaging contrast in tumours via the temporal integration of the imaging signals triggered by tumour acidosis. This method exploits the catastrophic disassembly, at the acidic pH of the tumour milieu, of pH-sensitive positron-emitting neutral copolymer micelles into polycationic polymers, which are then internalized and retained by the cancer cells. Positron emission tomography imaging of the 64Cu-labelled polymers detected small occult tumours (10–20 mm3) in the brain, head, neck and breast of mice at much higher contrast than 18F-fluorodeoxyglucose, 11C-methionine and pH-insensitive 64Cu-labelled nanoparticles. We also show that the pH-sensitive probes reduce false positive detection rates in a mouse model of non-cancerous lipopolysaccharide-induced inflammation. This macromolecular strategy for integrating tumour acidosis should enable improved cancer detection, surveillance and staging. The detection of small tumours with PET is significantly enhanced by temporal integration of the imaging signals, triggered by the acidic milieu of cancers, from pH-sensitive positron-emitting polycationic polymers.
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