Journal
NATURE BIOMEDICAL ENGINEERING
Volume 4, Issue 3, Pages 314-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41551-019-0416-1
Keywords
-
Categories
Funding
- NCI NIH HHS [U24 CA126608, R01 CA211930, R01 CA192221, P30 CA142543] Funding Source: Medline
Ask authors/readers for more resources
Owing to the diversity of cancer types and the spatiotemporal heterogeneity of tumour signals, high-resolution imaging of occult malignancy is challenging. F-18-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 Cu-64-labelled polymers detected small occult tumours (10-20 mm(3)) in the brain, head, neck and breast of mice at much higher contrast than F-18-fluorodeoxyglucose, C-11-methionine and pH-insensitive Cu-64-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available