title: Optical imaging of articular cartilage degeneration using near-infrared dipicolylamine probes.
abstract: Articular cartilage is the hydrated tissue that lines the ends of long bones in load bearing joints and provides joints with a smooth, nearly frictionless gliding surface. However, the deterioration of articular cartilage occurs in the early stages of osteoarthritis (OA) and is clinically and radiographically silent. Here two cationic near infrared fluorescent (NIRF) dipicolylamine (DPA) probes, Cy5-DPA-Zn and Cy7-DPA-Zn, were prepared for cartilage degeneration imaging and OA early detection through binding to the anionic glycosaminoglycans (GAGs). The feasibility of NIRF dye labeled DPA-Zn probes for cartilage degeneration imaging was examined ex vivo and in vivo. The ex vivo studies showed that Cy5-DPA-Zn and Cy7-DPA-Zn not only showed the high uptake and electrostatic attractive binding to cartilage, but also sensitively reflected the change of GAGs contents. In vivo imaging study further indicated that Cy5-DPA-Zn demonstrated higher uptake and retention in young mice (high GAGs) than old mice (low GAGs) when administrated via local injection in mouse knee joints. More importantly, Cy5-DPA-Zn showed dramatic higher signals in sham joint (high GAGs) than OA side (low GAGs), through sensitive reflecting the change of GAGs in the surgical induced OA models. In summary, Cy5-DPA-Zn provides promising visual detection for early cartilage pathological degeneration in living subjects.
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd., Lucas Expansion, P095, Stanford, CA 94305, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Immunology & Rheumatology, School of Medicine, Stanford, CA, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd., Lucas Expansion, P095, Stanford, CA 94305, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd., Lucas Expansion, P095, Stanford, CA 94305, USA.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd., Lucas Expansion, P095, Stanford, CA 94305, USA.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Qin
authors.affiliation: Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd., Lucas Expansion, P095, Stanford, CA 94305, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Immunology & Rheumatology, School of Medicine, Stanford, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Robinson
authors.affiliation: Molecular Targeting Technologies, Inc., West Chester, PA 19380, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gray
authors.affiliation: Molecular Targeting Technologies, Inc., West Chester, PA 19380, USA.
authors.forename: Koon Y
authors.initials: KY
authors.lastname: Pak
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: yuaixi666@hotmail.com.
authors.forename: Aixi
authors.initials: A
authors.lastname: Yu
authors.affiliation: Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd., Lucas Expansion, P095, Stanford, CA 94305, USA. Electronic address: zcheng@stanford.edu.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D000588:Amines / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007259:Infrared Rays; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D010848:Picolinic Acids / Q000737:chemistry / Q000378:metabolism
chemical_list: C501847:2,2'-dipicolylamine; D000588:Amines; D002232:Carbocyanines; D005456:Fluorescent Dyes; D006025:Glycosaminoglycans; D010848:Picolinic Acids; C085321:cyanine dye 5; C501744:indotricarbocyanine
keywords: Cartilage; Cartilage degeneration; Dipicolylamine probes; Glycosaminoglycans; Near infrared fluorescence imaging; Osteoarthritis