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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Veröffentlicht in:Nature nanotechnology Jg. 16; H. 6; S. 717 - 724
Hauptverfasser: 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
Sprache:Englisch
Veröffentlicht: England Nature Publishing Group 01.06.2021
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ISSN:1748-3387, 1748-3395, 1748-3395
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Abstract 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.
AbstractList 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.Ultra-high-frequency radio-frequency acoustic molecular imaging is a safe molecular imaging diagnostic option because it does not require radioactive probes or high magnetic fields, but lack of biocompatible targeted contrast agents has so far limited its in vivo application. In this paper the authors present perfluorocarbon nanodroplets containing hypertonic saline solution for targeted molecular imaging of prostate cancer in animal models.
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.
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.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.
Author Chen, Yun-Sheng
Chen, Dong-Hua
Dionne, Jennifer
Zhao, Yang
Stoyanova, Tanya
Beinat, Corinne
Hsu, En-Chi
Achterberg, Friso
Wang, Hanwei
Zlitni, Aimen
Gambhir, Sanjiv Sam
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  organization: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. yunsheng@illinois.edu
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  givenname: Yang
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  surname: Zhao
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  organization: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA
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  surname: Beinat
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  organization: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, USA
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  orcidid: 0000-0002-4790-1573
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  fullname: Chen, Dong-Hua
  organization: Department of Structural Biology, Stanford University, Stanford, CA, USA
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  givenname: Friso
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  surname: Achterberg
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  surname: Wang
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  organization: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA
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  givenname: Tanya
  orcidid: 0000-0003-0119-9747
  surname: Stoyanova
  fullname: Stoyanova, Tanya
  organization: Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA, USA
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  givenname: Jennifer
  orcidid: 0000-0001-5287-4357
  surname: Dionne
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  organization: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA
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  givenname: Sanjiv Sam
  orcidid: 0000-0002-2711-7554
  surname: Gambhir
  fullname: Gambhir, Sanjiv Sam
  organization: Department of Bioengineering, Stanford University, Stanford, CA, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33782588$$D View this record in MEDLINE/PubMed
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References 34903031 - J Urol. 2022 Mar;207(3):727-729. doi: 10.1097/JU.0000000000002363
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Snippet Molecular imaging is a crucial technique in clinical diagnostics but it relies on radioactive tracers or strong magnetic fields that are unsuitable for many...
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SubjectTerms 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
Title Ultra-high-frequency radio-frequency acoustic molecular imaging with saline nanodroplets in living subjects
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