Quantum dots-bevacizumab complexes for in vivo imaging of tumors.
OBJECTIVE
The basic role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab for first-line treatment of cancer patients. Recent anticancer therapeutics based on active tumor targeting by conjugating tumor-specific antibodies has become of great interest in oncology. Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers able to deliver specific molecule payloads in a selective manner to improve the efficacy and safety of cancer imaging and therapy. We herein aimed to determine the targeting ability of bevacizumab-conjugated quantum dots (QDs) in vitro and in vivo.


METHODS
We used QDs labeled with bevacizumab, in various in vitro experiments using cell lines derived from colorectal cancer (CRC) and breast cancer (BC). For a competition study of QD-bevacizumab complex and bevacizumab, the cells were pre-treated with bevacizumab (100 nmol/L) for 24 h before exposure to the QD-bevacizumab complex. The breast cancer cells (MDA-MB-231) were injected to 9 nude mice to make the xenograft tumor model. The QD-bevacizumab complex was injected into the tumor model and fluorescence measurements were performed at 1, 12, and 24 h post-injection.


RESULTS
Immunocytochemical data confirmed strong and specific binding of the QD-bevacizumab complex to the cell lines. The cells pre-treated with an excess of bevacizumab showed absence of QD binding. The in vivo fluorescence image disclosed that there was an increased signal of tumor after the injection of QDs. Ex vivo analysis showed 3.1 ± 0.8%, 28.6 ± 5.4% and 30.8 ± 4.2% injected dose/g accumulated in the tumors at 1, 12 and 24 h respectively. Tumor uptake was significantly decreased in the animals pretreated with excess of bevacizumab (p=0.001).


CONCLUSIONS
In conclusion, we could successfully detect the VEGF-expressing tumors using QDs-bevacizumab nanoprobes in vitro and in vivo, opening new perspectives for VEGF-targeted non-invasive imaging in clinical practice.
Department of Basic Biological Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece 2nd Department of Radiology, Attikon University Hospital, Athens, Greece mgazouli@med.uoa.gr.
Maria
M
Gazouli
Radiochemical Studies Laboratory, Institute of Nuclear and Radiological Sciences, Technology, Energy and Safety (I.N.Ra.S.T.E.S.) N.C.S.R. "Demokritos", Athens, Greece.
Penelope
P
Bouziotis
Department of Basic Biological Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
Anna
A
Lyberopoulou
Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science and Hydrobiology, Agricultural University of Athens, Athens, Greece.
John
J
Ikonomopoulos
Experimental and Research Center, ELPEN Pharma, Athens, Greece.
Apostolos
A
Papalois
Department of Basic Biological Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
Nicholas P
NP
Anagnou
2nd Department of Radiology, Attikon University Hospital, Athens, Greece.
Efstathios P
EP
Efstathopoulos
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000378:metabolism; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D058726:Nanoconjugates / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis*; D011485:Protein Binding; D045663:Quantum Dots / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D061067:Antibodies, Monoclonal, Humanized; D058726:Nanoconjugates; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
QDs; VEGF; bevacizumab; cancer; in vivo imaging