Quantitative imaging of disease signatures through radioactive decay signal conversion

Daniel L J Thorek, Anuja Ogirala, Bradley J. Beattie, Jan Grimm

Research output: Contribution to journalArticle

Abstract

In the era of personalized medicine, there is an urgent need for in vivo techniques able to sensitively detect and quantify molecular activities. Sensitive imaging of gamma rays is widely used; however, radioactive decay is a physical constant, and its signal is independent of biological interactions. Here, we introduce a framework of previously uncharacterized targeted and activatable probes that are excited by a nuclear decay-derived signal to identify and measure molecular signatures of disease. We accomplished this by using Cerenkov luminescence, the light produced by β-particle-emitting radionuclides such as clinical positron emission tomography (PET) tracers. Disease markers were detected using nanoparticles to produce secondary Cerenkov-induced fluorescence. This approach reduces background signal compared to conventional fluorescence imaging. In addition to tumor identification from a conventional PET scan, we demonstrate the medical utility of our approach by quantitatively determining prognostically relevant enzymatic activity. This technique can be applied to monitor other markers and represents a shift toward activatable nuclear medicine agents.

Original languageEnglish (US)
Pages (from-to)1345-1350
Number of pages6
JournalNature Medicine
Volume19
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Fingerprint

Positron emission tomography
Positron-Emission Tomography
Fluorescence
Nuclear medicine
Imaging techniques
Precision Medicine
Optical Imaging
Nuclear Medicine
Gamma Rays
Luminescence
Radioisotopes
Gamma rays
Nanoparticles
Radioactivity
Medicine
Tumors
Light
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Thorek, D. L. J., Ogirala, A., Beattie, B. J., & Grimm, J. (2013). Quantitative imaging of disease signatures through radioactive decay signal conversion. Nature Medicine, 19(10), 1345-1350. https://doi.org/10.1038/nm.3323

Quantitative imaging of disease signatures through radioactive decay signal conversion. / Thorek, Daniel L J; Ogirala, Anuja; Beattie, Bradley J.; Grimm, Jan.

In: Nature Medicine, Vol. 19, No. 10, 10.2013, p. 1345-1350.

Research output: Contribution to journalArticle

Thorek, DLJ, Ogirala, A, Beattie, BJ & Grimm, J 2013, 'Quantitative imaging of disease signatures through radioactive decay signal conversion', Nature Medicine, vol. 19, no. 10, pp. 1345-1350. https://doi.org/10.1038/nm.3323
Thorek, Daniel L J ; Ogirala, Anuja ; Beattie, Bradley J. ; Grimm, Jan. / Quantitative imaging of disease signatures through radioactive decay signal conversion. In: Nature Medicine. 2013 ; Vol. 19, No. 10. pp. 1345-1350.
@article{3f1b93bb68cf41bea06c91879e1babe6,
title = "Quantitative imaging of disease signatures through radioactive decay signal conversion",
abstract = "In the era of personalized medicine, there is an urgent need for in vivo techniques able to sensitively detect and quantify molecular activities. Sensitive imaging of gamma rays is widely used; however, radioactive decay is a physical constant, and its signal is independent of biological interactions. Here, we introduce a framework of previously uncharacterized targeted and activatable probes that are excited by a nuclear decay-derived signal to identify and measure molecular signatures of disease. We accomplished this by using Cerenkov luminescence, the light produced by β-particle-emitting radionuclides such as clinical positron emission tomography (PET) tracers. Disease markers were detected using nanoparticles to produce secondary Cerenkov-induced fluorescence. This approach reduces background signal compared to conventional fluorescence imaging. In addition to tumor identification from a conventional PET scan, we demonstrate the medical utility of our approach by quantitatively determining prognostically relevant enzymatic activity. This technique can be applied to monitor other markers and represents a shift toward activatable nuclear medicine agents.",
author = "Thorek, {Daniel L J} and Anuja Ogirala and Beattie, {Bradley J.} and Jan Grimm",
year = "2013",
month = "10",
doi = "10.1038/nm.3323",
language = "English (US)",
volume = "19",
pages = "1345--1350",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Quantitative imaging of disease signatures through radioactive decay signal conversion

AU - Thorek, Daniel L J

AU - Ogirala, Anuja

AU - Beattie, Bradley J.

AU - Grimm, Jan

PY - 2013/10

Y1 - 2013/10

N2 - In the era of personalized medicine, there is an urgent need for in vivo techniques able to sensitively detect and quantify molecular activities. Sensitive imaging of gamma rays is widely used; however, radioactive decay is a physical constant, and its signal is independent of biological interactions. Here, we introduce a framework of previously uncharacterized targeted and activatable probes that are excited by a nuclear decay-derived signal to identify and measure molecular signatures of disease. We accomplished this by using Cerenkov luminescence, the light produced by β-particle-emitting radionuclides such as clinical positron emission tomography (PET) tracers. Disease markers were detected using nanoparticles to produce secondary Cerenkov-induced fluorescence. This approach reduces background signal compared to conventional fluorescence imaging. In addition to tumor identification from a conventional PET scan, we demonstrate the medical utility of our approach by quantitatively determining prognostically relevant enzymatic activity. This technique can be applied to monitor other markers and represents a shift toward activatable nuclear medicine agents.

AB - In the era of personalized medicine, there is an urgent need for in vivo techniques able to sensitively detect and quantify molecular activities. Sensitive imaging of gamma rays is widely used; however, radioactive decay is a physical constant, and its signal is independent of biological interactions. Here, we introduce a framework of previously uncharacterized targeted and activatable probes that are excited by a nuclear decay-derived signal to identify and measure molecular signatures of disease. We accomplished this by using Cerenkov luminescence, the light produced by β-particle-emitting radionuclides such as clinical positron emission tomography (PET) tracers. Disease markers were detected using nanoparticles to produce secondary Cerenkov-induced fluorescence. This approach reduces background signal compared to conventional fluorescence imaging. In addition to tumor identification from a conventional PET scan, we demonstrate the medical utility of our approach by quantitatively determining prognostically relevant enzymatic activity. This technique can be applied to monitor other markers and represents a shift toward activatable nuclear medicine agents.

UR - http://www.scopus.com/inward/record.url?scp=84887479739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887479739&partnerID=8YFLogxK

U2 - 10.1038/nm.3323

DO - 10.1038/nm.3323

M3 - Article

C2 - 24013701

AN - SCOPUS:84887479739

VL - 19

SP - 1345

EP - 1350

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 10

ER -