A novel photoacoustic-fluorescent contrast agent for quantitative imaging of lymphatic drainage

Kirsten Cardinell; Neeru Gupta; Bryan D Koivisto; J Carl Kumaradas; Xun Zhou; Hyacinth Irving; Paola Luciani; Yeni H Yücel

doi:10.1016/j.pacs.2021.100239

A novel photoacoustic-fluorescent contrast agent for quantitative imaging of lymphatic drainage

Photoacoustics. 2021 Jan 8:21:100239. doi: 10.1016/j.pacs.2021.100239. eCollection 2021 Mar.

Authors

Kirsten Cardinell^{1

2

3}, Neeru Gupta^{1

2

4

5

6}, Bryan D Koivisto⁷, J Carl Kumaradas³, Xun Zhou^{1

2}, Hyacinth Irving¹, Paola Luciani⁸, Yeni H Yücel^{1

2

3

4

9

10}

Affiliations

¹ Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
² Department of Ophthalmology and Vision Sciences, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada.
³ Department of Physics, Faculty of Science, Ryerson University, Toronto, Ontario, Canada.
⁴ Department of Laboratory Medicine & Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
⁵ Glaucoma Unit, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
⁶ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada.
⁸ Department of Chemistry, Biochemistry, and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, CH-3012, Bern, Switzerland.
⁹ Institute of Biomedical Engineering, Science and Technology (iBEST), St. Michael's Hospital, Ryerson University, Toronto, Ontario, Canada.
¹⁰ Department of Mechanical Engineering, Faculty of Engineering and Architectural Science, Ryerson University, Toronto, Ontario, Canada.

Abstract

In vivo near-infrared (NIR) photoacoustic imaging (PAI) studies using novel contrast agents require validation, often via fluorescence imaging. Bioconjugation of NIR dyes to proteins is a versatile platform to obtain contrast agents for specific biomedical applications. Nonfluorescent NIR dyes with higher photostability present advantages for quantitative PAI, compared to most fluorescent NIR dyes. However, they don't provide a fluorescence signal required for fluorescence imaging. Here, we designed a hybrid PA-fluorescent contrast agent by conjugating albumin with a NIR nonfluorescent dye (QC-1) and a visible spectrum fluorescent dye, a BODIPY derivative. The new hybrid tracer QC-1/BSA/BODIPY (QBB) had a low minimum detectable concentration (2.5μM), a steep linear range (2.4-54.4 μM; slope 3.39 E -5), and high photostability. Tracer signal was measured in vivo using PAI to quantify its drainage from eye to the neck and its localization in the neck lymph node was validated with postmortem fluorescence imaging.

Keywords: Contrast agent; Fluorescence imaging; Limit of detection; Linear range; Lymphatic imaging; Minimum detectable concentration; Near-infrared; Photobleaching; Photostability.