Fluorescence labeled microbubbles for multimodal imaging

• Published in: Biochemical and biophysical research communications Vol. 464; no. 3; pp. 737 - 742
• Main Authors: Barrefelt, Åsa, Zhao, Ying, Larsson, Malin K., Egri, Gabriella, Kuiper, Raoul V., Hamm, Jörg, Saghafian, Maryam, Caidahl, Kenneth, Brismar, Torkel B., Aspelin, Peter, Heuchel, Rainer, Muhammed, Mamoun, Dähne, Lars, Hassan, Moustapha
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.08.2015
• Subjects: Animals; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Cell Line; Cell Line, Tumor; Contrast Media; Female; Fluorescence; Fluorescent Dyes; Heterografts; Humans; Imaging; Imaging, Three-Dimensional; In vivo imaging systems; Inbred C57BL; In vivo imaging systems; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Micro-computed tomography; Micro-ultrasound; Microbubbles; Multimodal Imaging - methods; Near infrared (NIR); Optical Imaging; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms/diagnosis/diagnostic imaging; Three-Dimensional; Tumor; Ultrasonography; VivoTag 680; X-Ray Microtomography; VivoTag 680; Near infrared (NIR); Micro-computed tomography; Microbubbles; Fluorescence; In vivo imaging systems; Micro-ultrasound
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2015.07.017

Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-μCT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging. •PVA-micro bubbles were labeled with NIR fluorescent to investigate biodistribution.•MB can visualize the surrounding pancreatic tissue but not inside the tumor mass.•MBs were distributed to the lungs, then redistributed to liver, spleen and kidneys.•MBs may have a potential use as theranostics for tumors located in liver and lungs.