[In-vivo targeted imaging of hepatocellular carcinoma in nude mice using quantum dot probes].
OBJECTIVE
To explore in-vivo targeted imaging techniques for liver cancer detection using quantum dots (QDs) labeled probes in a nude mouse model of human hepatocellular carcinoma.


METHODS
Mercaptoacetic acid (MAA) modified QDs were linked to mouse-anti-human alpha-fetoprotein (AFP) monoclonal antibody to form water soluble QD-AFP-Ab probes, which were validated by spectra analyses and transmission electron microscope. The probes were firstly used to detect AFP antigen in human hepatocellular carcinoma cell line HCCLM6 in-vitro by one-step immunofluorescence method. In-vivo tumor xenografts and lung metastases models were then established by inoculation of HCCLM6 cells subcutaneously and into the tail vein of nude mice, respectively. QD-AFP-Ab probes were injected into the tail vein of the tumor bearing mice for live animal fluorescence imaging. Spectra of tumor and normal tissue were analyzed under illumination of Ti: sapphire laser. Serum levels of alanine amino transferase, aspartate amino transferase, blood urea nitrogen and creatinine were determined by conventional biochemical analysis. The liver, spleen, lungs, kidneys, heart and brain of the experimental nude mice were investigated for nonspecific uptake of the probes by confocal microscope.


RESULTS
The QD-AFP-Ab probes had broad excitation spectra and high fluorescence intensity. They could specifically and efficiently recognize AFP antigen in hepatocellular carcinoma cells. Tumor targeting imaging using these probes were successful without any acute toxicity to the experimental animals. Spectra analysis showed that the probes per field were lower in the centre than the periphery of the tumor. Non-specific uptake of QD-AFP-Ab probes occurred mainly in the liver, spleen and lungs.


CONCLUSIONS
QD-AFP-Ab probes have good optical properties and biocompatibility for in-vivo targeted imaging of hepatocellular carcinoma. Such approach promises to be highly desirable for molecular targeted research of liver cancer.
Chen
Liang-dong
LD
Zhongnan Hospital of Wuhan University and Cancer Center of Wuhan University, Wuhan 430071, China.
Liu
Jia
J
Yu
Xue-feng
XF
Pang
Dai-wen
DW
Wang
Qu-quan
QQ
Yuan
Hong-yin
HY
Tang
Zhao-you
ZY
Li
Yan
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D015335:Molecular Probes / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D009368:Neoplasm Transplantation; D045663:Quantum Dots; D014018:Tissue Distribution; D000509:alpha-Fetoproteins / Q000276:immunology / Q000378:metabolism*