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http://dx.doi.org/10.3348/kjr.2013.14.1.30

In Vitro and In Vivo Imaging of Prostate Cancer Angiogenesis Using Anti-Vascular Endothelial Growth Factor Receptor 2 Antibody-Conjugated Quantum Dot  

Kwon, Haejin (Medicinal Chemistry Laboratory, Institute Pasteur Korea (IP-K))
Lee, Jiyeon (Medicinal Chemistry Laboratory, Institute Pasteur Korea (IP-K))
Song, Rita (Medicinal Chemistry Laboratory, Institute Pasteur Korea (IP-K))
Hwang, Sung Il (Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Institute of Radiation Medicine, Seoul National University Medical Research Center, Clinical Research Institute)
Lee, Junghan (Medicinal Chemistry Laboratory, Institute Pasteur Korea (IP-K))
Kim, Young-Hwa (Department of Nuclear Medicine and Biomedical Sciences Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine)
Lee, Hak Jong (Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Institute of Radiation Medicine, Seoul National University Medical Research Center, Clinical Research Institute)
Publication Information
Korean Journal of Radiology / v.14, no.1, 2013 , pp. 30-37 More about this Journal
Abstract
Objective: Authors aimed to determine the targeting ability of vascular endothelial growth factor receptor 2 (VEGFR2)- conjugated quantum dots (QDs) in vitro, and apply it for a xenograft prostate cancer mouse model. Materials and Methods: Conjugation reaction of QDs was performed by using the N-(3-dimethylaminopropyl)-N'- ethylcarbodiimide (EDC) and sulfo-(N-hydroxysulfosuccinimide) (Sulfo-NHS). The human umbilical vein cord endothelial cells (HUVECs) were incubated with QDs, conjugated with antiVGFR2, to see a specific binding in vitro. Fluorescent cell images were taken by a confocal microscope. The human prostate cancer cells (PC3) were injected to five nude mice on hind limbs to make the xenograft tumor model. QD-antiVEGFR2 antibody complex was injected into the tumor model and fluorescence measurements were performed at 1, 4, 9, 12, 15, and 24 hours after the injection. Results: The specific interaction between HUVECs and QD-antiVEGFR2 antibody was clearly shown in vitro. The in vivo fluorescence image disclosed that there was an increased signal of tumor, 12 hours after the injection of QDs. Conclusion: By showing endothelial cells binding with QDs-antiVEGFR2 antibodyand an experimental application of the antibody for VEGFR2 imaging in the prostate cancer xenograft mouse model, we suggests that the antibody-conjugated QDs can be a potential imaging tool for angiogenesis of the cancer.
Keywords
Quantum dot; VEGFR2; Angiogenesis; Prostate cancer; Near infrared;
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1 Cai, W, Shin, DW, Chen, K, Gheysens, O, Cao, Q, Wang, SX,Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects, Nano Lett, 6, 25, 669-676(2006)   DOI
2 Hardman, R,A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors, Environ Health Perspect, 114, 26, 165-172(2006)   DOI
3 Ipe, BI, Lehnig, M, Niemeyer, CM,On the generation of free radical species from quantum dots, Small, 1, 27, 706-709(2005)   DOI
4 Lovric, J, Cho, SJ, Winnik, FM, Maysinger, D,Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death, Chem Biol, 12, 28, 1227-1234(2005)   DOI
5 Jun, HY, Yin, HH, Kim, SH, Park, SH, Kim, HS, Yoon, KH,Visualization of tumor angiogenesis using MR imaging contrast agent Gd-DTPA-anti-VEGF receptor 2 antibody conjugate in a mouse tumor model, Korean J Radiol, 11, 29, 449-456(2010)   DOI
6 Ko, EY, Lee, SH, Kim, HH, Kim, SM, Shin, MJ, Kim, N,Evaluation of tumor angiogenesis with a second-generation US contrast medium in a rat breast tumor model, Korean J Radiol, 9, 30, 243-249(2008)   DOI
7 Kim, JW, Jeong, YY, Chang, NK, Heo, SH, Shin, SS, Lee, JH,Perfusion CT in colorectal cancer: comparison of perfusion parameters with tumor grade and microvessel density, Korean J Radiol, 13, 31, S89-S97(2012)   DOI
8 Kim, S, Lim, YT, Soltesz, EG, De Grand, AM, Lee, J, Nakayama, A,Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping, Nat Biotechnol, 22, 16, 93-97(2004)   DOI
9 Bentolila, LA, Ebenstein, Y, Weiss, S,Quantum dots for in vivo small-animal imaging, J Nucl Med, 50, 17, 493-496(2009)   DOI
10 Chen, K, Li, ZB, Wang, H, Cai, W, Chen, X,Dual-modality optical and positron emission tomography imaging of vascular endothelial growth factor receptor on tumor vasculature using quantum dots, Eur J Nucl Med Mol Imaging, 35, 18, 2235-2244(2008)   DOI
11 Zhang, H, Zeng, X, Li, Q, Gaillard-Kelly, M, Wagner, CR, Yee, D,Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore, Br J Cancer, 101, 19, 71-79(2009)   DOI
12 Chen, LD, Liu, J, Yu, XF, He, M, Pei, XF, Tang, ZY,The biocompatibility of quantum dot probes used for the targeted imaging of hepatocellular carcinoma metastasis, Biomaterials, 29, 20, 4170-4176(2008)   DOI
13 Weidner, N, Carroll, PR, Flax, J, Blumenfeld, W, Folkman, J,Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma, Am J Pathol, 143, 21, 401-409(1993)
14 Schlemmer, HP, Merkle, J, Grobholz, R, Jaeger, T, Michel, MS, Werner, A,Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens?, Eur Radiol, 14, 22, 309-317(2004)   DOI
15 Gao, X, Cui, Y, Levenson, RM, Chung, LW, Nie, S,In vivo cancer targeting and imaging with semiconductor quantum dots, Nat Biotechnol, 22, 23, 969-976(2004)   DOI
16 Cai, W, Chen, K, Li, ZB, Gambhir, SS, Chen, X,Dual-function probe for PET and near-infrared fluorescence imaging of tumor vasculature, J Nucl Med, 48, 24, 1862-1870(2007)   DOI
17 Massoud, TF, Gambhir, SS,Molecular imaging in living subjects: seeing fundamental biological processes in a new light, Genes Dev, 17, 6, 545-580(2003)   DOI
18 Mulder, WJ, Castermans, K, van Beijnum, JR, Oude Egbrink, MG, Chin, PT, Fayad, ZA,Molecular imaging of tumor angiogenesis using alphavbeta3-integrin targeted multimodal quantum dots, Angiogenesis, 12, 7, 17-24(2009)   DOI
19 Zhang, H, Yee, D, Wang, C,Quantum dots for cancer diagnosis and therapy: biological and clinical perspectives, Nanomedicine (Lond), 3, 8, 83-91(2008)   DOI
20 Willmann, JK, Paulmurugan, R, Chen, K, Gheysens, O, Rodriguez-Porcel, M, Lutz, AM,US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice, Radiology, 246, 9, 508-518(2008)   DOI
21 Deshpande, N, Pysz, MA, Willmann, JK,Molecular ultrasound assessment of tumor angiogenesis, Angiogenesis, 13, 13, 175-188(2010)   DOI
22 Yang, YA, Wu, H, Williams, KR, Cao, YC,Synthesis of CdSe and CdTe nanocrystals without precursor injection, Angew Chem Int Ed Engl, 44, 10, 6712-6715(2005)   DOI
23 Lee, J, Choi, Y, Kim, K, Hong, S, Park, HY, Lee, T,Characterization and cancer cell specific binding properties of anti-EGFR antibody conjugated quantum dots, Bioconjug Chem, 21, 11, 940-946(2010)   DOI
24 Schellenberger, EA, Bogdanov, A, Petrovsky, A, Ntziachristos, V, Weissleder, R, Josephson, L,Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy, Neoplasia, 5, 12, 187-192(2003)   DOI
25 Hicklin, DJ, Ellis, LM,Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis, J Clin Oncol, 23, 14, 1011-1027(2005)   DOI
26 Smith, AM, Duan, H, Mohs, AM, Nie, S,Bioconjugated quantum dots for in vivo molecular and cellular imaging, Adv Drug Deliv Rev, 60, 15, 1226-1240(2008)   DOI
27 Folkman, J,Tumor angiogenesis: therapeutic implications, N Engl J Med, 285, 1, 1182-1186(1971)   DOI
28 Oostendorp, M, Douma, K, Hackeng, TM, Dirksen, A, Post, MJ, van Zandvoort, MA,Quantitative molecular magnetic resonance imaging of tumor angiogenesis using cNGR-labeled paramagnetic quantum dots, Cancer Res, 68, 2, 7676-7683(2008)   DOI
29 Carmeliet, P,Angiogenesis in health and disease, Nat Med, 9, 3, 653-660(2003)   DOI
30 Meitar, D, Crawford, SE, Rademaker, AW, Cohn, SL,Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma, J Clin Oncol, 14, 4, 405-414(1996)   DOI
31 Daldrup, H, Shames, DM, Wendland, M, Okuhata, Y, Link, TM, Rosenau, W,Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media, AJR Am J Roentgenol, 171, 5, 941-949(1998)   DOI