Assessment of unspecific near-infrared dyes in laser-induced fluorescence imaging of experimental arthritis.
OBJECTIVE
The aim of the study is to evaluate in vivo fluorescence imaging of experimental inflammatory joint disease by applying two different near-infrared (NIR) dyes in a model of Borrelia-induced Lyme arthritis.


METHODS
Forty mice, 20 with Lyme arthritis and 20 controls, were examined. Two nonspecific NIR carbocyanine dyes, indocyanine green (ICG) and a hydrophilic carbocyanine derivative (1,1'-bis-[4-sulfobutyl] indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium salt [SIDAG]), were administered intravenously at two doses. Fluorescence images were acquired before and during 120 seconds after injection of cyanine dyes. For both dyes, the area under the curve (AUC) was determined for the interval between 40 and 80 seconds after injection. In addition, the slope of the signal decrease was compared among animal groups. Results were compared with histological findings.


RESULTS
The general temporal fluorescence intensity course for ICG was characterized by a rapid increase, with a peak at 40-50 seconds followed by a decrease; conversely for SIDAG, by a slow increase. AUC analysis for both dyes showed that the fluorescence signal differed significantly between controls and arthritic animals (P < .05). Within these groups, there were significant differences between the two doses investigated. ICG differed significantly between control and arthritic animals in the slope of the signal decrease for both doses investigated (P < .05). Histological examination showed early stages of inflammation in arthritic animals.


CONCLUSIONS
NIR fluorescence imaging based on the pharmacokinetic behavior of ICG or SIDAG is a promising approach to detect inflammatory joint changes of experimental arthritis. Moreover, SIDAG is suited to differentiate inflammatory and noninflammatory joints 24 hours after dye application.
Fischer
Thomas
T
Department of Radiology, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20/21, 10098 Berlin, Germany. thom.fischer@charite.de
Gemeinhardt
Ines
I
Wagner
Susanne
S
Stieglitz
Dorothee V
DV
Schnorr
Jörg
J
Hermann
Kay-Geert A
KG
Ebert
Bernd
B
Petzelt
Diethard
D
Macdonald
Rainer
R
Licha
Kai
K
Schirner
Michael
M
Krenn
Veit
V
Kamradt
Thomas
T
Taupitz
Matthias
M
D000818:Animals; D019540:Area Under Curve; D001169:Arthritis, Experimental / Q000175:diagnosis*; D002232:Carbocyanines; D004396:Coloring Agents; D003287:Contrast Media; D005453:Fluorescence; D007208:Indocyanine Green; D007834:Lasers; D008193:Lyme Disease / Q000175:diagnosis; D051379:Mice; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D018709:Statistics, Nonparametric
C430879:1,1'-bis-(4-sulfobutyl)indotricarbocyanine-5,5'-dicarboxylic acid diglucamide; D002232:Carbocyanines; D004396:Coloring Agents; D003287:Contrast Media; D007208:Indocyanine Green