Multimodality labeling strategies for the investigation of nanocrystalline cellulose biodistribution in a mouse model of breast cancer

Tutkimustuotos: Lehtiartikkeli

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Multimodality labeling strategies for the investigation of nanocrystalline cellulose biodistribution in a mouse model of breast cancer. / Sarparanta, Mirkka; Pourat, Jacob; Carnazza, Kathryn E.; Tang, Jun; Paknejad, Navid; Reiner, Thomas; Kostiainen, Mauri A.; Lewis, Jason S.

julkaisussa: NUCLEAR MEDICINE AND BIOLOGY, Vuosikerta 80-81, 01.01.2020, s. 1-12.

Tutkimustuotos: Lehtiartikkeli

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Sarparanta, Mirkka ; Pourat, Jacob ; Carnazza, Kathryn E. ; Tang, Jun ; Paknejad, Navid ; Reiner, Thomas ; Kostiainen, Mauri A. ; Lewis, Jason S. / Multimodality labeling strategies for the investigation of nanocrystalline cellulose biodistribution in a mouse model of breast cancer. Julkaisussa: NUCLEAR MEDICINE AND BIOLOGY. 2020 ; Vuosikerta 80-81. Sivut 1-12.

Bibtex - Lataa

@article{5066fd863cc647bd978edcccf27bdc58,
title = "Multimodality labeling strategies for the investigation of nanocrystalline cellulose biodistribution in a mouse model of breast cancer",
abstract = "Methods: We have developed a nuclear and fluorescence labeling strategy for nanocrystalline cellulose (CNC), an emerging biomaterial with versatile chemistry and facile preparation from renewable sources. We modified CNC through 1,1′-carbonyldiimidazole (CDI) activation with radiometal chelators desferrioxamine B and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), allowing for the labeling with zirconium-89 (t½ = 78.41 h) and copper-64 (t½ = 12.70 h), respectively, for non-invasive positron emission tomography (PET) imaging. The far-red fluorescent dye Cy5 was added for ex vivo optical imaging, microscopy and flow cytometry. The multimodal CNC were evaluated in the syngeneic orthotopic 4T1 tumor model of human stage IV breast cancer. Results: Modified CNC exhibited low cytotoxicity in RAW 264.7 macrophages over 96 h, and high radiolabel stability in vitro. After systemic administration, radiolabeled CNC were rapidly sequestered to the organs of the reticulo-endothelial system (RES), indicating immune recognition and no passive tumor targeting by the enhanced permeability and retention (EPR) effect. Modification with NOTA was a more favorable strategy in terms of radiolabeling yield, specific radioactivity, and both the radiolabel and dispersion stability in physiological conditions. Flow cytometry analysis of Cy5-positive immune cells from the spleen and tumor corroborated the uptake of CNC to phagocytic cells. Conclusions: Future studies on the in vivo behavior of CNC should be concentrated on improving the nanomaterial stability and circulation half-life under physiological conditions and optimizing further the labeling yields for the multimodality imaging strategy presented. Advances in knowledge: Our studies constitute one of the first accounts of a multimodality nuclear and fluorescent probe for the evaluation of CNC biodistribution in vivo and outline the pitfalls in radiometal labeling strategies for future evaluation of targeted CNC-based drug delivery systems. Implications for patient care: Quantitative and sensitive molecular imaging methods provide information on the structure–activity relationships of the nanomaterial and guide the translation from in vitro models to clinically relevant animal models.",
keywords = "Biodistribution, Imaging, Labeling, Multimodality, Nanocrystalline cellulose, Positron emission tomography (PET)",
author = "Mirkka Sarparanta and Jacob Pourat and Carnazza, {Kathryn E.} and Jun Tang and Navid Paknejad and Thomas Reiner and Kostiainen, {Mauri A.} and Lewis, {Jason S.}",
year = "2020",
month = "1",
day = "1",
doi = "10.1016/j.nucmedbio.2019.11.002",
language = "English",
volume = "80-81",
pages = "1--12",
journal = "NUCLEAR MEDICINE AND BIOLOGY",
issn = "0969-8051",
publisher = "Elsevier Inc.",

}

RIS - Lataa

TY - JOUR

T1 - Multimodality labeling strategies for the investigation of nanocrystalline cellulose biodistribution in a mouse model of breast cancer

AU - Sarparanta, Mirkka

AU - Pourat, Jacob

AU - Carnazza, Kathryn E.

AU - Tang, Jun

AU - Paknejad, Navid

AU - Reiner, Thomas

AU - Kostiainen, Mauri A.

AU - Lewis, Jason S.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Methods: We have developed a nuclear and fluorescence labeling strategy for nanocrystalline cellulose (CNC), an emerging biomaterial with versatile chemistry and facile preparation from renewable sources. We modified CNC through 1,1′-carbonyldiimidazole (CDI) activation with radiometal chelators desferrioxamine B and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), allowing for the labeling with zirconium-89 (t½ = 78.41 h) and copper-64 (t½ = 12.70 h), respectively, for non-invasive positron emission tomography (PET) imaging. The far-red fluorescent dye Cy5 was added for ex vivo optical imaging, microscopy and flow cytometry. The multimodal CNC were evaluated in the syngeneic orthotopic 4T1 tumor model of human stage IV breast cancer. Results: Modified CNC exhibited low cytotoxicity in RAW 264.7 macrophages over 96 h, and high radiolabel stability in vitro. After systemic administration, radiolabeled CNC were rapidly sequestered to the organs of the reticulo-endothelial system (RES), indicating immune recognition and no passive tumor targeting by the enhanced permeability and retention (EPR) effect. Modification with NOTA was a more favorable strategy in terms of radiolabeling yield, specific radioactivity, and both the radiolabel and dispersion stability in physiological conditions. Flow cytometry analysis of Cy5-positive immune cells from the spleen and tumor corroborated the uptake of CNC to phagocytic cells. Conclusions: Future studies on the in vivo behavior of CNC should be concentrated on improving the nanomaterial stability and circulation half-life under physiological conditions and optimizing further the labeling yields for the multimodality imaging strategy presented. Advances in knowledge: Our studies constitute one of the first accounts of a multimodality nuclear and fluorescent probe for the evaluation of CNC biodistribution in vivo and outline the pitfalls in radiometal labeling strategies for future evaluation of targeted CNC-based drug delivery systems. Implications for patient care: Quantitative and sensitive molecular imaging methods provide information on the structure–activity relationships of the nanomaterial and guide the translation from in vitro models to clinically relevant animal models.

AB - Methods: We have developed a nuclear and fluorescence labeling strategy for nanocrystalline cellulose (CNC), an emerging biomaterial with versatile chemistry and facile preparation from renewable sources. We modified CNC through 1,1′-carbonyldiimidazole (CDI) activation with radiometal chelators desferrioxamine B and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), allowing for the labeling with zirconium-89 (t½ = 78.41 h) and copper-64 (t½ = 12.70 h), respectively, for non-invasive positron emission tomography (PET) imaging. The far-red fluorescent dye Cy5 was added for ex vivo optical imaging, microscopy and flow cytometry. The multimodal CNC were evaluated in the syngeneic orthotopic 4T1 tumor model of human stage IV breast cancer. Results: Modified CNC exhibited low cytotoxicity in RAW 264.7 macrophages over 96 h, and high radiolabel stability in vitro. After systemic administration, radiolabeled CNC were rapidly sequestered to the organs of the reticulo-endothelial system (RES), indicating immune recognition and no passive tumor targeting by the enhanced permeability and retention (EPR) effect. Modification with NOTA was a more favorable strategy in terms of radiolabeling yield, specific radioactivity, and both the radiolabel and dispersion stability in physiological conditions. Flow cytometry analysis of Cy5-positive immune cells from the spleen and tumor corroborated the uptake of CNC to phagocytic cells. Conclusions: Future studies on the in vivo behavior of CNC should be concentrated on improving the nanomaterial stability and circulation half-life under physiological conditions and optimizing further the labeling yields for the multimodality imaging strategy presented. Advances in knowledge: Our studies constitute one of the first accounts of a multimodality nuclear and fluorescent probe for the evaluation of CNC biodistribution in vivo and outline the pitfalls in radiometal labeling strategies for future evaluation of targeted CNC-based drug delivery systems. Implications for patient care: Quantitative and sensitive molecular imaging methods provide information on the structure–activity relationships of the nanomaterial and guide the translation from in vitro models to clinically relevant animal models.

KW - Biodistribution

KW - Imaging

KW - Labeling

KW - Multimodality

KW - Nanocrystalline cellulose

KW - Positron emission tomography (PET)

UR - http://www.scopus.com/inward/record.url?scp=85075185015&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2019.11.002

DO - 10.1016/j.nucmedbio.2019.11.002

M3 - Article

VL - 80-81

SP - 1

EP - 12

JO - NUCLEAR MEDICINE AND BIOLOGY

JF - NUCLEAR MEDICINE AND BIOLOGY

SN - 0969-8051

ER -

ID: 39178568