Ultra-high-frequency radio-frequency acoustic molecular imaging with saline nanodroplets in living subjects

Molecular imaging is a crucial technique in clinical diagnostics but it relies on radioactive tracers or strong magnetic fields that are unsuitable for many patients, particularly infants and pregnant women. Ultra-high-frequency radio-frequency acoustic (UHF-RF-acoustic) imaging using non-ionizing R...

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Bibliographic Details
Published in:Nature nanotechnology Vol. 16; no. 6; pp. 717 - 724
Main Authors: Chen, Yun-Sheng, Zhao, Yang, Beinat, Corinne, Zlitni, Aimen, Hsu, En-Chi, Chen, Dong-Hua, Achterberg, Friso, Wang, Hanwei, Stoyanova, Tanya, Dionne, Jennifer, Gambhir, Sanjiv Sam
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.06.2021
Subjects:
Acoustic imaging
Acoustics
Animal models
Animals
Biocompatibility
Cell Line, Tumor
Chemical synthesis
Contrast agents
Contrast media
Contrast Media - chemistry
Drug Stability
Gastrin
Humans
Hydrocarbons, Fluorinated - chemistry
Iron oxides
Magnetic fields
Male
Medical imaging
Mice
Mice, Inbred NOD
Molecular Imaging - instrumentation
Molecular Imaging - methods
Nanoparticles
Nanostructures - chemistry
Perfluorocarbons
Phantoms, Imaging
Prostate cancer
Prostatic Neoplasms - diagnostic imaging
Prostatic Neoplasms - metabolism
Radio frequency
Radio Waves
Radioactive tracers
Receptors
Receptors, Bombesin - genetics
Receptors, Bombesin - immunology
Receptors, Bombesin - metabolism
Saline Solution, Hypertonic - chemistry
Saline solutions
Spatial discrimination
Spatial resolution
Ultrahigh frequencies
Xenograft Model Antitumor Assays
Xenografts
Xenotransplantation
ISSN:1748-3387, 1748-3395, 1748-3395
Online Access:Get full text
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Summary:Molecular imaging is a crucial technique in clinical diagnostics but it relies on radioactive tracers or strong magnetic fields that are unsuitable for many patients, particularly infants and pregnant women. Ultra-high-frequency radio-frequency acoustic (UHF-RF-acoustic) imaging using non-ionizing RF pulses allows deep-tissue imaging with sub-millimetre spatial resolution. However, lack of biocompatible and targetable contrast agents has prevented the successful in vivo application of UHF-RF-acoustic imaging. Here we report our development of targetable nanodroplets for UHF-RF-acoustic molecular imaging of cancers. We synthesize all-liquid nanodroplets containing hypertonic saline that are stable for at least 2 weeks and can produce high-intensity UHF-RF-acoustic signals. Compared with concentration-matched iron oxide nanoparticles, our nanodroplets produce at least 1,600 times higher UHF-RF-acoustic signals at the same imaging depth. We demonstrate in vivo imaging using the targeted nanodroplets in a prostate cancer xenograft mouse model expressing gastrin release protein receptor (GRPR), and show that targeting specificity is increased by more than 2-fold compared with untargeted nanodroplets or prostate cancer cells not expressing this receptor.
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ISSN:1748-3387
1748-3395
1748-3395
DOI:10.1038/s41565-021-00869-5