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Multimodal Imaging of Pancreatic Ductal Adenocarcinoma Using Multifunctional Nanoparticles as Contrast Agents
Karolinska Inst, Div Expt Canc Med, Dept Lab Med LABMED, SE-14186 Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Clin Res Ctr, SE-14186 Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Ctr Allogene Stem Cell Transplantat CAST, SE-14186 Stockholm, Sweden..
Karolinska Inst, Div Expt Canc Med, Dept Lab Med LABMED, SE-14186 Stockholm, Sweden..
Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Med Imaging & Technol, SE-14186 Stockholm, Sweden..
Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Pancreat Canc Res Lab, SE-14186 Stockholm, Sweden..
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2020 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 12, no 48, p. 53665-53681Article in journal (Refereed) Published
Abstract [en]

Late diagnosis and refractory behavior toward current treatment protocols make pancreatic ductal adenocarcinoma (PDAC) one of the most difficult cancer forms to treat. The imaging-based approach plays an important role to identify potentially curable PDAC patients in high-risk groups at the early stage. In the present study, we developed a core-shell structured gold nanorod (AuNR) as a contrast agent for multimodal imaging and investigated its application for PDAC diagnosis. The composite nanopartides composed of a AuNR core inside a layer of mesoporous silica that was then coated with a gadolinium oxide carbonate shell (AuNR-SiO2 -Gd) are designed to be used in magnetic resonance imaging (MRI), X-ray computed tomography (CT), and photoacoustic imaging (PM). A phantom study with the AuNR-SiO2-Gd NPs demonstrated higher MRI contrast compared to Gadovist and higher X-ray attenuation than Visipaque. A strong, stable, and broad wavelength range signal with a peak at 800 nm was observed in PAI. The AuNR-SiO2-Gd NPs showed significant contrast enhancement under PAI/MRI/CT in both the liver and spleen of control mice after intravenous administration. The utility in PDAC was studied in a genetically engineered mouse model carrying Kras and p53 mutations, which develops spontaneous tumors and keeps the desmoplasia and hypovascularity feature of PDAC in patients. The AuNR-SiO2-Gd NPs were highly accumulated in the surrounding soft tissues but were sparsely distributed throughout the tumor due to dense stroma infiltration and poor tumor vascularization. Hence, a negative contrast within the tumor area in CT/PAI and a positive contrast in MRI were observed. In conclusion, AuNR-SiO2-Gd NPs have good potential to be developed as a multimodal contrast agent for PDAC, which might improve early diagnosis and benefit the clinical outcome for PDAC patients.

Place, publisher, year, edition, pages
American Chemical Society (ACS) , 2020. Vol. 12, no 48, p. 53665-53681
Keywords [en]
multimodal, magnetic resonance imaging, computed tomography, photoacoustic imaging, pancreatic ductal adenocarcinoma
National Category
Cancer and Oncology
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URN: urn:nbn:se:kth:diva-289087DOI: 10.1021/acsami.0c15430ISI: 000596876400009PubMedID: 33201660Scopus ID: 2-s2.0-85096661158OAI: oai:DiVA.org:kth-289087DiVA, id: diva2:1521783
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QC 20210125

Available from: 2021-01-25 Created: 2021-01-25 Last updated: 2022-06-25Bibliographically approved

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Dutta, JoydeepMuhammed, Mamoun

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