title: In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe.
abstract: Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases, although the exact mechanism is yet to be explored. Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care. The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe. Herein, we report the first in vivo CB2R-targeted NIR inflammation imaging study using a synthetic fluorescent probe developed in our laboratory, NIR760-mbc94. In vitro binding assay and fluorescence microscopy study indicate NIR760-mbc94 specifically binds towards CB2R in mouse RAW264.7 macrophage cells. Furthermore, in vivo imaging was performed using a Complete Freund's Adjuvant (CFA)-induced inflammation mouse model. NIR760-mbc94 successfully identified inflamed tissues and the probe uptake was blocked by a CB2R ligand, SR144528. Additionally, immunofluorescence staining in cryosectioned tissues validated the NIR760-mbc94 uptake in inflamed tissues. In conclusion, this study reports the first in vivo CB2R-targeted inflammation imaging using an NIR fluorescent probe. Specific targeting of NIR760-mbc94 has been demonstrated in macrophage cells, as well as a CFA-induced inflammation mouse model. The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases.
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh Pittsburgh, PA 15219, USA.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh Pittsburgh, PA 15219, USA.
authors.forename: Pin
authors.initials: P
authors.lastname: Shao
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh Pittsburgh, PA 15219, USA.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Ling
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh Pittsburgh, PA 15219, USA ; Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University Shanghai, 200032, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Division of Surgical Oncology and Department of Immunology, University of Pittsburgh Cancer Institute Pittsburgh, PA 15213, USA.
authors.forename: Weizhou
authors.initials: W
authors.lastname: Hou
authors.affiliation: Division of Surgical Oncology and Department of Immunology, University of Pittsburgh Cancer Institute Pittsburgh, PA 15213, USA.
authors.forename: Steve H
authors.initials: SH
authors.lastname: Thorne
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh Pittsburgh, PA 15219, USA.
authors.forename: Wissam
authors.initials: W
authors.lastname: Beaino
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh Pittsburgh, PA 15219, USA ; Department of Bioengineering, University of Pittsburgh Pittsburgh, PA 15261, USA ; University of Pittsburgh Cancer Institute Pittsburgh, PA 15232, USA.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.affiliation: Department of Biostatistics, University of Pittsburgh Pittsburgh, PA 15261, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh Pittsburgh, PA 15219, USA ; Department of Bioengineering, University of Pittsburgh Pittsburgh, PA 15261, USA ; University of Pittsburgh Cancer Institute Pittsburgh, PA 15232, USA.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Bai
keywords: CB2; Inflammation; cannabinoid receptor; fluorescent probe; near infrared; optical imaging