TY - JOUR
T1 - Glucosamine-linked near-infrared fluorescent probes for imaging of solid tumor xenografts
AU - Korotcov, Alexandru V.
AU - Ye, Yunpeng
AU - Chen, Yue
AU - Zhang, Fayun
AU - Huang, Sophia
AU - Lin, Stephen
AU - Sridhar, Rajagopalan
AU - Achilefu, Samuel
AU - Wang, Paul C.
N1 - Funding Information:
Acknowledgment. This work was supported by grants from DOD USAMRMC W81XWH-10-1-0767 and NIH/NCRR RCMI 2G12 RR003048.
PY - 2012/8
Y1 - 2012/8
N2 - Purpose: Near-infrared fluorescence (NIRF) imaging is an attractive technique for studying diseases at the molecular level in vivo. Glucose transporters are often used as targets for in vivo imaging of tumors. The efficiency of a tumor-seeking fluorescent probe can be enhanced by attaching one ormore glucosamine (GlcN)moieties. This study was designed to evaluate the use of previously developed GlcN-linked NIRF probes for in vitro and in vivo optical imaging of cancer. Procedures: Cellular uptake of the probes (1 μM) was investigated in monolayer cultures of luciferase-expressing PC3 (PC3-luc) cells. The prostate tumors were established as subcutaneous xenografts using PC3-luc cells in nude mice. The biodistributions and tumor-targeting specificities of cypate (cyp), cypate-D-(+)-glucosamine (cyp-GlcN), and D-(+)-gluosaminecypate- D-(+)-gluosamine (cyp-2GlcN) were studied. The tumor, muscle, and major organs were collected for ex vivo optical imaging. Results: The tumor cell uptake of the probe containing two glucosamine residues, cyp-2GlcN, was significantly higher than the uptake of both the probe with one glucosamine residue, cyp- GlcN, and the probe without glucosamine, cyp only. Similarly, in in vivo experiments, cyp-2GlcN demonstrated higher maximum fluorescence intensity and longer residence lifetime in tumors than cyp-GlcN or cyp. The ex vivo biodistribution analysis revealed that tumor uptake of cyp- 2GlcN and cyp-GlcN was four- and twofold higher than that of cyp at 24 h post-injection, respectively. Conclusion: Both cyp-GlcN and cyp-2GlcN NIRF probes exhibited good tumor-targeting properties in prostate cancer cell cultures and live mice. The cyp-2GlcN probe showed the highest uptake with good retention characteristics in vivo. The uptake of cyp-2GlcN and cyp- GlcN is likely mediated by glucosamine-recognizing transporters. The uptake mechanism is being explored further for developing cypate-glucosamine-based probes for in vivo imaging.
AB - Purpose: Near-infrared fluorescence (NIRF) imaging is an attractive technique for studying diseases at the molecular level in vivo. Glucose transporters are often used as targets for in vivo imaging of tumors. The efficiency of a tumor-seeking fluorescent probe can be enhanced by attaching one ormore glucosamine (GlcN)moieties. This study was designed to evaluate the use of previously developed GlcN-linked NIRF probes for in vitro and in vivo optical imaging of cancer. Procedures: Cellular uptake of the probes (1 μM) was investigated in monolayer cultures of luciferase-expressing PC3 (PC3-luc) cells. The prostate tumors were established as subcutaneous xenografts using PC3-luc cells in nude mice. The biodistributions and tumor-targeting specificities of cypate (cyp), cypate-D-(+)-glucosamine (cyp-GlcN), and D-(+)-gluosaminecypate- D-(+)-gluosamine (cyp-2GlcN) were studied. The tumor, muscle, and major organs were collected for ex vivo optical imaging. Results: The tumor cell uptake of the probe containing two glucosamine residues, cyp-2GlcN, was significantly higher than the uptake of both the probe with one glucosamine residue, cyp- GlcN, and the probe without glucosamine, cyp only. Similarly, in in vivo experiments, cyp-2GlcN demonstrated higher maximum fluorescence intensity and longer residence lifetime in tumors than cyp-GlcN or cyp. The ex vivo biodistribution analysis revealed that tumor uptake of cyp- 2GlcN and cyp-GlcN was four- and twofold higher than that of cyp at 24 h post-injection, respectively. Conclusion: Both cyp-GlcN and cyp-2GlcN NIRF probes exhibited good tumor-targeting properties in prostate cancer cell cultures and live mice. The cyp-2GlcN probe showed the highest uptake with good retention characteristics in vivo. The uptake of cyp-2GlcN and cyp- GlcN is likely mediated by glucosamine-recognizing transporters. The uptake mechanism is being explored further for developing cypate-glucosamine-based probes for in vivo imaging.
KW - Cypate
KW - Glucosamine
KW - Near-infrared fluorescence
KW - Optical imaging
KW - Prostate cancer
KW - Tumor
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U2 - 10.1007/s11307-011-0520-4
DO - 10.1007/s11307-011-0520-4
M3 - Article
C2 - 21971932
AN - SCOPUS:84865507369
SN - 1536-1632
VL - 14
SP - 443
EP - 451
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 4
ER -