A biomarker-responsive T2ex MRI contrast agent

Iman Daryaei; Edward A. Randtke; Mark D. Pagel

doi:10.1002/mrm.26250

A biomarker-responsive T_2ex MRI contrast agent

Iman Daryaei, Edward A. Randtke, Mark D. Pagel

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Purpose: This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T₂ exchange (T_2ex) properties after interacting with a molecular biomarker. Methods: The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O₂. The R₁ and R₂ relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r_2ex relaxivities. Results: The reaction of Tm-DO3A-oAA with NO and O₂ caused a 6.4-fold increase in the r₂ relaxivity of the agent, whereas r₁ relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T_2ex agent. The effects of pH and temperature on the r₂ relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand. Conclusions: T_2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665–1670, 2017.

Original language	English (US)
Pages (from-to)	1665-1670
Number of pages	6
Journal	Magnetic resonance in medicine
Volume	77
Issue number	4
DOIs	https://doi.org/10.1002/mrm.26250
State	Published - Apr 1 2017
Externally published	Yes

Keywords

T2ex MRI
chemical exchange: molecular imaging
nitric oxide
responsive agent

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

Access to Document

10.1002/mrm.26250

Cite this

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title = "A biomarker-responsive T2ex MRI contrast agent",

abstract = "Purpose: This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T2 exchange (T2ex) properties after interacting with a molecular biomarker. Methods: The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O2. The R1 and R2 relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r2ex relaxivities. Results: The reaction of Tm-DO3A-oAA with NO and O2 caused a 6.4-fold increase in the r2 relaxivity of the agent, whereas r1 relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T2ex agent. The effects of pH and temperature on the r2 relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand. Conclusions: T2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665–1670, 2017.",

keywords = "T2ex MRI, chemical exchange: molecular imaging, nitric oxide, responsive agent",

author = "Iman Daryaei and Randtke, {Edward A.} and Pagel, {Mark D.}",

note = "Funding Information: The authors thank Dr. Katrina Miranda and Dr. Joel Jorolan for access to NO gas, and Dr. Josef Vagner and Renata Patek for access to HPLC. This research was supported by NIH grants R01 CA169774 and P50 CA95060. Publisher Copyright: {\textcopyright} 2016 International Society for Magnetic Resonance in Medicine",

year = "2017",

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doi = "10.1002/mrm.26250",

language = "English (US)",

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T1 - A biomarker-responsive T2ex MRI contrast agent

AU - Daryaei, Iman

AU - Randtke, Edward A.

AU - Pagel, Mark D.

N1 - Funding Information: The authors thank Dr. Katrina Miranda and Dr. Joel Jorolan for access to NO gas, and Dr. Josef Vagner and Renata Patek for access to HPLC. This research was supported by NIH grants R01 CA169774 and P50 CA95060. Publisher Copyright: © 2016 International Society for Magnetic Resonance in Medicine

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Purpose: This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T2 exchange (T2ex) properties after interacting with a molecular biomarker. Methods: The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O2. The R1 and R2 relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r2ex relaxivities. Results: The reaction of Tm-DO3A-oAA with NO and O2 caused a 6.4-fold increase in the r2 relaxivity of the agent, whereas r1 relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T2ex agent. The effects of pH and temperature on the r2 relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand. Conclusions: T2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665–1670, 2017.

AB - Purpose: This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T2 exchange (T2ex) properties after interacting with a molecular biomarker. Methods: The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O2. The R1 and R2 relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r2ex relaxivities. Results: The reaction of Tm-DO3A-oAA with NO and O2 caused a 6.4-fold increase in the r2 relaxivity of the agent, whereas r1 relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T2ex agent. The effects of pH and temperature on the r2 relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand. Conclusions: T2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665–1670, 2017.

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