Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization.
We have synthesized a group of glucamine and gluosamine-substituted cyanine dyes structurally related to indocyanine green (ICG) and have characterized these compounds with regard to their potential as contrast agents for biomedical optical imaging. The compounds reported herein exhibit increased hydrophilicity and less plasma protein binding (< 50%), and are thus expected to have different pharmacokinetic properties compared with ICG. Furthermore, we measured enhanced fluorescence quantum yields (7-15%) in a physiological environment with respect to ICG. For the derivative with the highest hydrophilicity (5a) the efflux from tumor and normal tissue was monitored by intensity-modulated diffuse optical spectroscopy after intravenous injection into tumor-bearing rats. In comparison with ICG, 5a exhibited a considerably enhanced tissue-efflux half-life (73 min versus less than 10 min for ICG in tumor tissue), a two-fold higher initial tissue absorption coefficient compared to ICG, and finally, it generated an elevated tumor-to-tissue concentration gradient up to 1 h after injection. In conclusion, compounds such as 5a are promising contrast agents for optical imaging, and could facilitate highly sensitive and specific detection of breast cancer or other malignancies by utilizing mechanisms similar to contrast-enhanced magnetic resonance imaging or computerized tomography.
Licha
K
K
Institut für Diagnostikforschung GmbH, Freien Universität Berlin, Germany. kai.licha@charite.de
Riefke
B
B
Ntziachristos
V
V
Becker
A
A
Chance
B
B
Semmler
W
W
D000818:Animals; D001932:Brain Neoplasms / Q000737:chemistry*; D004396:Coloring Agents / Q000737:chemistry*; D003287:Contrast Media; D005910:Glioma / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D019265:Spectroscopy, Near-Infrared
D004396:Coloring Agents; D003287:Contrast Media