Quantification and biodistribution of iron oxide nanoparticles in the primary clearance organs of mice using T1 contrast for heating

Jinjin Zhang; Hattie L. Ring; Katie R. Hurley; Qi Shao; Cathy S. Carlson; Djaudat Idiyatullin; Navid Manuchehrabadi; P. Jack Hoopes; Christy L. Haynes; John C. Bischof; Michael Garwood

doi:10.1002/mrm.26394

Quantification and biodistribution of iron oxide nanoparticles in the primary clearance organs of mice using T₁ contrast for heating

Jinjin Zhang, Hattie L. Ring, Katie R. Hurley, Qi Shao, Cathy S. Carlson, Djaudat Idiyatullin, Navid Manuchehrabadi, P. Jack Hoopes, Christy L. Haynes, John C. Bischof, Michael Garwood

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Abstract

Purpose: To use contrast based on longitudinal relaxation times (T₁) or rates (R₁) to quantify the biodistribution of iron oxide nanoparticles (IONPs), which are of interest for hyperthermia therapy, cell targeting, and drug delivery, within primary clearance organs. Methods: Mesoporous silica-coated IONPs (msIONPs) were intravenously injected into 15 naïve mice. Imaging and mapping of the longitudinal relaxation rate constant at 24 h or 1 week postinjection were performed with an echoless pulse sequence (SWIFT). Alternating magnetic field heating measurements were also performed on ex vivo tissues. Results: Signal enhancement from positive T₁ contrast caused by IONPs was observed and quantified in vivo in liver, spleen, and kidney at concentrations up to 3.2 mg Fe/(g tissue wt.) (61 mM Fe). In most cases, each organ had a linear correlation between the R₁ and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R₁ and volumetric SAR in hyperthermia therapy was observed. Conclusion: The linear dependence between R₁ and tissue iron concentration in major organs allows quantitative monitoring of IONP biodistribution in a dosage range relevant to magnetic hyperthermia applications, which falls into the concentration gap between CT and conventional MRI techniques. Magn Reson Med 78:702–712, 2017.

Original language	English (US)
Pages (from-to)	702-712
Number of pages	11
Journal	Magnetic resonance in medicine
Volume	78
Issue number	2
DOIs	https://doi.org/10.1002/mrm.26394
State	Published - Aug 2017

Bibliographical note

Funding Information:
Drs. Zhang and Ring contributed equally to this work. K.H. acknowledges support from an NSF Graduate Research Fellowship. Q.S. acknowledges support from the University of Minnesota IEM Cancer Animal Core Lab. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. Histologic services were provided by the Histology and Immunohistochemistry (IHC) Laboratory, University of Minnesota. Histologic imaging was provided by the Digital Imaging Facility, BioNet, University of Minnesota. The authors thank Z. Gao and N. Klein for their valuable discussion; L. Utecht for her support with animal care; F. Zhou for her support with transmission electron microscopy sample preparation; R. Knurr for his support with ICP-OES acquisition; and C. Forster for her support with histology.

Publisher Copyright:
© 2016 International Society for Magnetic Resonance in Medicine.

Keywords

SWIFT
biodistribution
hyperthermia
iron oxide nanoparticle
primary clearance organs

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10.1002/mrm.26394

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366089

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Zhang, J., Ring, H. L., Hurley, K. R., Shao, Q., Carlson, C. S., Idiyatullin, D., Manuchehrabadi, N., Hoopes, P. J., Haynes, C. L., Bischof, J. C., & Garwood, M. (2017). Quantification and biodistribution of iron oxide nanoparticles in the primary clearance organs of mice using T₁ contrast for heating. Magnetic resonance in medicine, 78(2), 702-712. https://doi.org/10.1002/mrm.26394

Zhang, J, Ring, HL, Hurley, KR, Shao, Q , Carlson, CS , Idiyatullin, D, Manuchehrabadi, N, Hoopes, PJ, Haynes, CL , Bischof, JC & Garwood, M 2017, 'Quantification and biodistribution of iron oxide nanoparticles in the primary clearance organs of mice using T₁ contrast for heating', Magnetic resonance in medicine, vol. 78, no. 2, pp. 702-712. https://doi.org/10.1002/mrm.26394

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abstract = "Purpose: To use contrast based on longitudinal relaxation times (T1) or rates (R1) to quantify the biodistribution of iron oxide nanoparticles (IONPs), which are of interest for hyperthermia therapy, cell targeting, and drug delivery, within primary clearance organs. Methods: Mesoporous silica-coated IONPs (msIONPs) were intravenously injected into 15 na{\"i}ve mice. Imaging and mapping of the longitudinal relaxation rate constant at 24 h or 1 week postinjection were performed with an echoless pulse sequence (SWIFT). Alternating magnetic field heating measurements were also performed on ex vivo tissues. Results: Signal enhancement from positive T1 contrast caused by IONPs was observed and quantified in vivo in liver, spleen, and kidney at concentrations up to 3.2 mg Fe/(g tissue wt.) (61 mM Fe). In most cases, each organ had a linear correlation between the R1 and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R1 and volumetric SAR in hyperthermia therapy was observed. Conclusion: The linear dependence between R1 and tissue iron concentration in major organs allows quantitative monitoring of IONP biodistribution in a dosage range relevant to magnetic hyperthermia applications, which falls into the concentration gap between CT and conventional MRI techniques. Magn Reson Med 78:702–712, 2017.",

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author = "Jinjin Zhang and Ring, {Hattie L.} and Hurley, {Katie R.} and Qi Shao and Carlson, {Cathy S.} and Djaudat Idiyatullin and Navid Manuchehrabadi and Hoopes, {P. Jack} and Haynes, {Christy L.} and Bischof, {John C.} and Michael Garwood",

note = "Funding Information: Drs. Zhang and Ring contributed equally to this work. K.H. acknowledges support from an NSF Graduate Research Fellowship. Q.S. acknowledges support from the University of Minnesota IEM Cancer Animal Core Lab. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. Histologic services were provided by the Histology and Immunohistochemistry (IHC) Laboratory, University of Minnesota. Histologic imaging was provided by the Digital Imaging Facility, BioNet, University of Minnesota. The authors thank Z. Gao and N. Klein for their valuable discussion; L. Utecht for her support with animal care; F. Zhou for her support with transmission electron microscopy sample preparation; R. Knurr for his support with ICP-OES acquisition; and C. Forster for her support with histology. Publisher Copyright: {\textcopyright} 2016 International Society for Magnetic Resonance in Medicine.",

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AU - Zhang, Jinjin

AU - Ring, Hattie L.

AU - Hurley, Katie R.

AU - Shao, Qi

AU - Carlson, Cathy S.

AU - Idiyatullin, Djaudat

AU - Manuchehrabadi, Navid

AU - Hoopes, P. Jack

AU - Haynes, Christy L.

AU - Bischof, John C.

AU - Garwood, Michael

N1 - Funding Information: Drs. Zhang and Ring contributed equally to this work. K.H. acknowledges support from an NSF Graduate Research Fellowship. Q.S. acknowledges support from the University of Minnesota IEM Cancer Animal Core Lab. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. Histologic services were provided by the Histology and Immunohistochemistry (IHC) Laboratory, University of Minnesota. Histologic imaging was provided by the Digital Imaging Facility, BioNet, University of Minnesota. The authors thank Z. Gao and N. Klein for their valuable discussion; L. Utecht for her support with animal care; F. Zhou for her support with transmission electron microscopy sample preparation; R. Knurr for his support with ICP-OES acquisition; and C. Forster for her support with histology. Publisher Copyright: © 2016 International Society for Magnetic Resonance in Medicine.

PY - 2017/8

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N2 - Purpose: To use contrast based on longitudinal relaxation times (T1) or rates (R1) to quantify the biodistribution of iron oxide nanoparticles (IONPs), which are of interest for hyperthermia therapy, cell targeting, and drug delivery, within primary clearance organs. Methods: Mesoporous silica-coated IONPs (msIONPs) were intravenously injected into 15 naïve mice. Imaging and mapping of the longitudinal relaxation rate constant at 24 h or 1 week postinjection were performed with an echoless pulse sequence (SWIFT). Alternating magnetic field heating measurements were also performed on ex vivo tissues. Results: Signal enhancement from positive T1 contrast caused by IONPs was observed and quantified in vivo in liver, spleen, and kidney at concentrations up to 3.2 mg Fe/(g tissue wt.) (61 mM Fe). In most cases, each organ had a linear correlation between the R1 and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R1 and volumetric SAR in hyperthermia therapy was observed. Conclusion: The linear dependence between R1 and tissue iron concentration in major organs allows quantitative monitoring of IONP biodistribution in a dosage range relevant to magnetic hyperthermia applications, which falls into the concentration gap between CT and conventional MRI techniques. Magn Reson Med 78:702–712, 2017.

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