An in-vivo pilot study into the effects of FDG-mNP in cancer in mice

Omer Aras, Gillian Pearce, Adam J. Watkins, Fuad Nurili, Emin Ilker Medine, Ozge Kozgus Guldu, Volkan Tekin, Julian Wong, Xianghong Ma, Richard Ting, Perihan Unak, Oguz Akin, Bing Xu

Research output: Contribution to journalArticle

Abstract

Purpose

Previously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice.

Materials and methods

FDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points.

Results

In prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months.

Conclusion

Intravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.
Original languageEnglish
Article numbere0202482
JournalPLoS ONE
Volume13
Issue number8
DOIs
Publication statusPublished - 20 Aug 2018

Fingerprint

Magnetite Nanoparticles
magnetite
nanoparticles
Glucose
glucose
neoplasms
prostatic neoplasms
Tumors
mice
Prostate
Neoplasms
Bearings (structural)
Tissue
injection
Injections
Cells
Liver
fever
spleen
Fever

Bibliographical note

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Funding: This research was funded by Memorial Sloan Kettering Cancer Centre, Department of Radiology, and the NIH/NCI Cancer Center Support Grant P30 CA008748, NIH Small-Animal Imaging Research Program (SAIRP), R24 CA83084; NIH Prostate SPORE, P50-CA92629; Ege University, Institute of Nuclear Sciences, Department of Nuclear Applications, 35100 Turkey; School of Engineering and Applied Science, Aston University, Birmingham, UK, B4 7E and Mr Julian Wong FRCS, Division of Vascular & Endovascular Surgery Department of Cardiac, Thoracic & Vascular Surgery National University Heart Centre, Singapore 1E Kent Ridge Road NUHS Tower Block, Level 9, Singapore 119228.

Cite this

Aras, O., Pearce, G., Watkins, A. J., Nurili, F., Medine, E. I., Guldu, O. K., ... Xu, B. (2018). An in-vivo pilot study into the effects of FDG-mNP in cancer in mice. PLoS ONE, 13(8), [e0202482]. https://doi.org/10.1371/journal.pone.0202482
Aras, Omer ; Pearce, Gillian ; Watkins, Adam J. ; Nurili, Fuad ; Medine, Emin Ilker ; Guldu, Ozge Kozgus ; Tekin, Volkan ; Wong, Julian ; Ma, Xianghong ; Ting, Richard ; Unak, Perihan ; Akin, Oguz ; Xu, Bing. / An in-vivo pilot study into the effects of FDG-mNP in cancer in mice. In: PLoS ONE. 2018 ; Vol. 13, No. 8.
@article{0497c6094e6840fe98f877cf72dca017,
title = "An in-vivo pilot study into the effects of FDG-mNP in cancer in mice",
abstract = "PurposePreviously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice.Materials and methodsFDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points.ResultsIn prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months.ConclusionIntravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.",
author = "Omer Aras and Gillian Pearce and Watkins, {Adam J.} and Fuad Nurili and Medine, {Emin Ilker} and Guldu, {Ozge Kozgus} and Volkan Tekin and Julian Wong and Xianghong Ma and Richard Ting and Perihan Unak and Oguz Akin and Bing Xu",
note = "This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: This research was funded by Memorial Sloan Kettering Cancer Centre, Department of Radiology, and the NIH/NCI Cancer Center Support Grant P30 CA008748, NIH Small-Animal Imaging Research Program (SAIRP), R24 CA83084; NIH Prostate SPORE, P50-CA92629; Ege University, Institute of Nuclear Sciences, Department of Nuclear Applications, 35100 Turkey; School of Engineering and Applied Science, Aston University, Birmingham, UK, B4 7E and Mr Julian Wong FRCS, Division of Vascular & Endovascular Surgery Department of Cardiac, Thoracic & Vascular Surgery National University Heart Centre, Singapore 1E Kent Ridge Road NUHS Tower Block, Level 9, Singapore 119228.",
year = "2018",
month = "8",
day = "20",
doi = "10.1371/journal.pone.0202482",
language = "English",
volume = "13",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

Aras, O, Pearce, G, Watkins, AJ, Nurili, F, Medine, EI, Guldu, OK, Tekin, V, Wong, J, Ma, X, Ting, R, Unak, P, Akin, O & Xu, B 2018, 'An in-vivo pilot study into the effects of FDG-mNP in cancer in mice', PLoS ONE, vol. 13, no. 8, e0202482. https://doi.org/10.1371/journal.pone.0202482

An in-vivo pilot study into the effects of FDG-mNP in cancer in mice. / Aras, Omer; Pearce, Gillian; Watkins, Adam J.; Nurili, Fuad; Medine, Emin Ilker; Guldu, Ozge Kozgus; Tekin, Volkan; Wong, Julian; Ma, Xianghong; Ting, Richard; Unak, Perihan; Akin, Oguz; Xu, Bing.

In: PLoS ONE, Vol. 13, No. 8, e0202482, 20.08.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An in-vivo pilot study into the effects of FDG-mNP in cancer in mice

AU - Aras, Omer

AU - Pearce, Gillian

AU - Watkins, Adam J.

AU - Nurili, Fuad

AU - Medine, Emin Ilker

AU - Guldu, Ozge Kozgus

AU - Tekin, Volkan

AU - Wong, Julian

AU - Ma, Xianghong

AU - Ting, Richard

AU - Unak, Perihan

AU - Akin, Oguz

AU - Xu, Bing

N1 - This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: This research was funded by Memorial Sloan Kettering Cancer Centre, Department of Radiology, and the NIH/NCI Cancer Center Support Grant P30 CA008748, NIH Small-Animal Imaging Research Program (SAIRP), R24 CA83084; NIH Prostate SPORE, P50-CA92629; Ege University, Institute of Nuclear Sciences, Department of Nuclear Applications, 35100 Turkey; School of Engineering and Applied Science, Aston University, Birmingham, UK, B4 7E and Mr Julian Wong FRCS, Division of Vascular & Endovascular Surgery Department of Cardiac, Thoracic & Vascular Surgery National University Heart Centre, Singapore 1E Kent Ridge Road NUHS Tower Block, Level 9, Singapore 119228.

PY - 2018/8/20

Y1 - 2018/8/20

N2 - PurposePreviously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice.Materials and methodsFDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points.ResultsIn prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months.ConclusionIntravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.

AB - PurposePreviously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice.Materials and methodsFDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points.ResultsIn prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months.ConclusionIntravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.

UR - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202482

U2 - 10.1371/journal.pone.0202482

DO - 10.1371/journal.pone.0202482

M3 - Article

VL - 13

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 8

M1 - e0202482

ER -

Aras O, Pearce G, Watkins AJ, Nurili F, Medine EI, Guldu OK et al. An in-vivo pilot study into the effects of FDG-mNP in cancer in mice. PLoS ONE. 2018 Aug 20;13(8). e0202482. https://doi.org/10.1371/journal.pone.0202482