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A Library of Potential Nanoparticle Contrast Agents for X-Ray Fluorescence Tomography Bioimaging
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.ORCID iD: 0000-0002-9637-970X
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.ORCID iD: 0000-0003-3095-0608
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2018 (English)In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, article id UNSP 8174820Article in journal (Refereed) Published
Abstract [en]

Nanoparticles (NPs) have been used as contrast agents for several bioimaging modalities. X-ray fluorescence (XRF) tomography can provide sensitive and quantitative 3D detection of NPs. With spectrally matched NPs as contrast agents, we demonstrated earlier in a laboratory system that XRF tomography could achieve high-spatial-resolution tumor imaging in mice. Here, we present the synthesis, characterization, and evaluation of a library of NPs containing Y, Zr, Nb, Rh, and Ru that have spectrally matched K-shell absorption for the laboratory scale X-ray source. The K-shell emissions of these NPs are spectrally well separated from the X-ray probe and the Compton background, making them suitable for the lab-scale XRF tomography system. Their potential as XRF contrast agents is demonstrated successfully in a small-animal equivalent phantom, confirming the simulation results. The diversity in the NP composition provides a flexible platform for a better design and biological optimization of XRF tomography nanoprobes.

Place, publisher, year, edition, pages
WILEY-HINDAWI , 2018. article id UNSP 8174820
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:kth:diva-242269DOI: 10.1155/2018/8174820ISI: 000455608200001PubMedID: 30686945Scopus ID: 2-s2.0-85059939967OAI: oai:DiVA.org:kth-242269DiVA, id: diva2:1284931
Note

QC 20190201

Available from: 2019-02-01 Created: 2019-02-01 Last updated: 2024-03-15Bibliographically approved
In thesis
1. Synthesis and Characterization of Nanoprobes for X-Ray Fluorescence Computed Tomography (XFCT) Bio-imaging
Open this publication in new window or tab >>Synthesis and Characterization of Nanoprobes for X-Ray Fluorescence Computed Tomography (XFCT) Bio-imaging
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

X-ray fluorescence computed tomography (XFCT) is an emerging biomedical imaging technique. The KTH-XFCT laboratory system offers a characteristic 24 keV emission line, and high spatial resolution (200 𝜇m) images. XFCT as a newly emerging modality also requires the exploration and development of suitable contrast agents. Nanomaterials have been widely used as contrast agents in many popular imaging modalities like MRI, PET, and CT. They have several advantages including long blood circulation time, high ratio of surface area to volume, and enhanced image contrast. However, the use of nanomaterials as contrast agents is limited by their biocompatibility and toxicity, which are determined by the physicochemical properties including size, morphology, surface chemistry. Therefore, the study on the synthesis and characterization of nanomaterials is an indispensable step. In this thesis, a group of elements (Y, Zr, Nb, Ru, Rh) are selected based on the X-ray K𝛼-absorption energy, matching with the 24 keV emission line of KTH-XFCT source. Y, Zr, Nb, Ru and Rh based nanoparticles are synthesized by hydrothermal and polyol method, identified as the ceramic and metallic groups. XRF performance is demonstrated by the XFCT system. Metallic Ru and Rh nanoparticles are further selected to study the synthesis conditions and in vitro toxicity for their smaller TEM and hydrodynamic size. Surface properties are investigated to show the isoelectric point and polymer coating on the metallic nanoparticles. Morphological different Rh nanoparticles are obtained by introducing different additives during the synthesis, indicating the different cytotoxicity performance attributed to different morphologies. Silica coating is further performed on the surface of metallic and metallic nanoparticles to improve their biocompatibility. The in vitro toxicity assessment are performed on the murine macrophages and human ovarian cancer cell lines. X-ray fluorescence performance is evaluated for each nanoparticles by using soft-tissue equivalent holder and in situ small-animal imaging experiments. The results indicates the spatial resolution and detection sensitivity of the concentration of the metallic nanoparticles. In this work, we demonstrate the potential of a group selected nanomaterials as XFCT contrast agents for the first time, especially, investigate the synthesis, surface properties, in vitro toxicity as well as detection sensitivity of the metallic nanoparticles.

Abstract [sv]

Röntgenfluorescenstomografi (XFCT) är en ny och lovande teknik för biomedicinsk avbildning. Det kompakta KTH-XFCT systemet har en röntgenemission på 24 keV och möjliggör avbildning med hög spatial upplösning (200 𝜇m). Eftersom XFCT är en ny modalitet behövs forskning och utveckling av lämpliga kontrastmedel. Nanomaterial har använts brett som kontrastmedel inom många etablerade avbildningstekniker, så som magnetresonanstomografi (MR), positronemissionstomografi (PET) och datortomografi (CT). Nanomaterial har flera fördelar jämfört med traditionella kontrastmedel, exempelvis längre blodcirkulationstider, större yta per volym och överlag förbättrad kontrast. Däremot begränsas användningen av nanomaterial som kontrastmedel av egenskaper såsom biokompatibilitet och toxicitet vilket bestäms av fysikokemikaliska egenskaper såsom storlek, morfologi och ytkemi. Därför är studier av syntes samt karakterisering av nanomaterial viktigt för biomedicinska tillämpningar. I denna avhandling har en grupp grundämnen (Y, Zr, Nb, Ru, Rh) valts ut baserat på att deras K-absorptionskanter matchar röntgenemissionen på 24 keV hos KTH-XFCT systemet. Y, Zr, Nb, Ru och Rh nanopartiklar synteserades med hydrotermiska samt polyol-metoder och klassades som antingen keramiska eller metalliska nanopartiklar. Röntgenfluorescensen från nanopartiklarna påvisades med KTH-XFCT systemet. De metalliska nanopartiklarna med mindre storlek baserade på Ru och Rh valdes ut och studerades närmare i termer av syntesparametrar samt in vitro toxicitet i cellkulturer. Ytegenskaper hos dessa metalliska nanopartiklar undersöktes för att uppvisa deras isoelektriska punkter samt PVP-ytskikt. Morfologiskt kontrollerbara Rh nanopartiklar tillverkades genom att introducera olika tillsatser under syntesprocessen, vilket sedan användes för att påvisa att cytotoxiciteten är morfologi-beroende. Ytan hos de metalliska nanopartiklarna modifierades med ett skikt av kiseldioxid för att ytterligare förbättra biokompatibiliteten. Murina makrofager och mänskliga cellinjer för äggstockscancer användes för att evaluera toxiciteten in vitro. Röntgenfluorescensavbildning med nanopartiklarna demonstrerades både med hjälp av mjukvävnad-liknande fantomer samt med in situ experiment i avlivna möss. Resultaten indikerade både spatial upplösning och observerbar koncentration av ackumulerade nanopartiklar i KTH-XFCT systemet. I detta arbete demonstreras för första gången potentialen hos en grupp utvalda nanomaterial som kontrastmedel för XFCT. Detta arbete inkluderar studier av syntes, ytkemi, in vitro toxicitet samt detektionssensitiviteten hos de metalliska nanopartiklarna.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2020. p. 67
Series
TRITA-SCI-FOU ; 2020:36
National Category
Biomaterials Science Inorganic Chemistry Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-286262 (URN)978-91-7873-705-5 (ISBN)
Public defence
2020-12-18, Via Zoom https://kth-se.zoom.us/j/69899182230, Stockholm, 14:00 (English)
Opponent
Supervisors
Available from: 2020-11-25 Created: 2020-11-23 Last updated: 2024-03-27Bibliographically approved

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Li, YuyangShaker, KianLarsson, Jakob C.Vogt, CarmenHertz, Hans M.Toprak, Muhammet S.

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