Serial non-invasive monitoring of renal disease following immune-mediated injury using near-infrared optical imaging.
BACKGROUND
Non-invasive monitoring of disease progression in kidney disease is still a major challenge in clinical practice. In vivo near-infrared (NIR) imaging provides a new tool for studying disease mechanisms and non-invasive monitoring of disease development, even in deep organs. The LI-COR IRDye® 800CW RGD optical probe (RGD probe) is a NIR fluorophore, that can target integrin alpha v beta 3 (α(v)β(3)) in tissues.


OBJECTIVE
This study aims to monitor renal disease progression in an anti-glomerular basement membrane (GBM) nephritis mouse model.


METHODS
Anti-GBM nephritis was induced in 129x1/svJ mice by anti-GBM serum challenge. The expression of integrin α(v)β(3) in the diseased kidney was examined by immunohistochemistry and quantitative polymerase chain reaction. The RGD probe and control fluorophores, the 800CW dye, and the BSA-conjugated 800CW dye, were administered into anti-GBM nephritic mice. LI-COR Pearl® Impulse imaging system was used for in vivo imaging; while ex vivo organ imaging was acquired using the Maestro(TM) imaging system.


RESULTS
Kidney tissue from anti-GBM nephritic mice showed higher levels of integrin α(v)β(3) expression at both the protein and the mRNA level compared to normal mice. The RGD probe allowed in vivo renal imaging and the fluorescent signal could be specifically captured in the diseased kidneys up to 14 days, reflecting longitudinal changes in renal function.


CONCLUSIONS
The infrared RGD molecular probe that tracks integrin expression can be successfully used to monitor renal disease progression following immune-mediated nephritis.
Internal Medicine/Rheumatology, University of Texas, Southwestern Medical Center, Dallas, Texas, USA.
Yong
Y
Du
Shion
S
An
Li
L
Liu
Li
L
Li
Xin J
XJ
Zhou
Ralph P
RP
Mason
Chandra
C
Mohan
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D005456:Fluorescent Dyes; D015870:Gene Expression; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000032:analysis* / Q000235:genetics*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology*; D007700:Kinetics; D051379:Mice; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D061848:Optical Imaging / Q000295:instrumentation / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors
D001323:Autoantibodies; D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; C051951:antiglomerular basement membrane antibody