Near IR heptamethine cyanine dye-mediated cancer imaging.
OBJECTIVE
Near-IR fluorescence imaging has great potential for noninvasive in vivo imaging of tumors. In this study, we show the preferential uptake and retention of two hepatamethine cyanine dyes, IR-783 and MHI-148, in tumor cells and tissues.


METHODS
IR-783 and MHI-148 were investigated for their ability to accumulate in human cancer cells, tumor xenografts, and spontaneous mouse tumors in transgenic animals. Time- and concentration-dependent dye uptake and retention in normal and cancer cells and tissues were compared, and subcellular localization of the dyes and mechanisms of the dye uptake and retention in tumor cells were evaluated using organelle-specific tracking dyes and bromosulfophthalein, a competitive inhibitor of organic anion transporting peptides. These dyes were used to detect human cancer metastases in a mouse model and differentiate cancer cells from normal cells in blood.


RESULTS
These near-IR hepatamethine cyanine dyes were retained in cancer cells but not normal cells, in tumor xenografts, and in spontaneous tumors in transgenic mice. They can be used to detect cancer metastasis and cancer cells in blood with a high degree of sensitivity. The dyes were found to concentrate in the mitochondria and lysosomes of cancer cells, probably through organic anion transporting peptides, because the dye uptake and retention in cancer cells can be blocked completely by bromosulfophthalein. These dyes, when injected to mice, did not cause systemic toxicity.


CONCLUSIONS
These two heptamethine cyanine dyes are promising imaging agents for human cancers and can be further exploited to improve cancer detection, prognosis, and treatment.
Yang
Xiaojian
X
Molecular Urology and Therapeutics, Department of Urology, Winship Cancer Institute, Atlanta, GA, USA.
Shi
Chunmeng
C
Tong
Rong
R
Qian
Weiping
W
Zhau
Haiyen E
HE
Wang
Ruoxiang
R
Zhu
Guodong
G
Cheng
Jianjun
J
Yang
Vincent W
VW
Cheng
Tianmin
T
Henary
Maged
M
Strekowski
Lucjan
L
Chung
Leland W K
LW
D000818:Animals; D002232:Carbocyanines / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000175:diagnosis*; D019265:Spectroscopy, Near-Infrared; D014183:Transplantation, Heterologous
D002232:Carbocyanines; D005456:Fluorescent Dyes
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