PET imaging of occult tumours by temporal integration of tumour-acidosis signals from pH-sensitive 64Cu-labelled polymers

Gang Huang, Tian Zhao, Chensu Wang, Kien Nham, Yahong Xiong, Xiaofei Gao, Yihui Wang, Guiyang Hao, Wuping Ge, Xiankai Sun, Baran D Sumer, Jinming Gao

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalNature Biomedical Engineering
DOIs
StatePublished - Jan 1 2019

Fingerprint

Acidosis
Tumors
Polymers
Imaging techniques
Neoplasms
Positron emission tomography
Fluorodeoxyglucose F18
Micelles
Positrons
Positron-Emission Tomography
Methionine
Amplification
Lipopolysaccharides
Brain
Copolymers
Cells
Nanoparticles
Breast
Neck
Head

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

Cite this

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title = "PET imaging of occult tumours by temporal integration of tumour-acidosis signals from pH-sensitive 64Cu-labelled polymers",
abstract = "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.",
author = "Gang Huang and Tian Zhao and Chensu Wang and Kien Nham and Yahong Xiong and Xiaofei Gao and Yihui Wang and Guiyang Hao and Wuping Ge and Xiankai Sun and Sumer, {Baran D} and Jinming Gao",
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AU - Huang, Gang

AU - Zhao, Tian

AU - Wang, Chensu

AU - Nham, Kien

AU - Xiong, Yahong

AU - Gao, Xiaofei

AU - Wang, Yihui

AU - Hao, Guiyang

AU - Ge, Wuping

AU - Sun, Xiankai

AU - Sumer, Baran D

AU - Gao, Jinming

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

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