Multimodal Imaging of Pancreatic Ductal Adenocarcinoma Using Multifunctional Nanoparticles as Contrast Agents

Ying Zhao; Fei Ye; Torkel B Brismar; Xuan Li; Rui He; Rainer Heuchel; Ramy El-Sayed; Neus Feliu; Wenyi Zheng; Sandra Oerther; Joydeep Dutta; Wolfgang J Parak; Mamoun Muhammed; Moustapha Hassan

doi:10.1021/acsami.0c15430

Multimodal Imaging of Pancreatic Ductal Adenocarcinoma Using Multifunctional Nanoparticles as Contrast Agents

ACS Appl Mater Interfaces. 2020 Dec 2;12(48):53665-53681. doi: 10.1021/acsami.0c15430. Epub 2020 Nov 17.

Authors

Ying Zhao^{1

2}, Fei Ye^{1

3}, Torkel B Brismar⁴, Xuan Li⁵, Rui He^{1

2}, Rainer Heuchel⁵, Ramy El-Sayed¹, Neus Feliu^{1

6}, Wenyi Zheng^{1

2}, Sandra Oerther^{1

2}, Joydeep Dutta³, Wolfgang J Parak⁶, Mamoun Muhammed^{3

7}, Moustapha Hassan^{1

2

7}

Affiliations

¹ Division of Experimental Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden.
² Clinical Research Center, and Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital-Huddinge, SE-141 86 Stockholm, Sweden.
³ KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
⁴ Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden.
⁵ Pancreatic Cancer Research Laboratory, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden.
⁶ Center for Hybrid Nanostructures (CHyN), University of Hamburg, 22607 Hamburg, Germany.
⁷ Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria 21526, Egypt.

Abstract

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 nanoparticles 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 (PAI). 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.

Keywords: computed tomography; magnetic resonance imaging; multimodal; pancreatic ductal adenocarcinoma; photoacoustic imaging.