JBNB  Vol.4 No.1 , January 2013
Synthesis and Development of Gd3+-ALGDG2-C595 as MR Imaging Contrast Agent
Abstract: Magnetic Resonance imaging (MR imaging) as a powerful non-invasive modality is of high global interest for early cancer detection. The aim of this study was the synthesis of nanodendrimer and its conjugate with monoclonal antibody C595 against breast cancer cell, followed by its chelating with gadolinium for its magnetic property. First, anti-MUC-1 monoclonal antibody C595 was coupled to a biodegradable biocompatible Anionic Linear Globular Dendrimer G2 (having polyethylene glycol core and citric acid shell). Then prepared nanocomplex loaded by gadolinium to make novel agent of functional MR imaging. Anticancer effects and MR imaging parameters of the prepared nanoconjugate was investigated under in vitro conditions doing performing several studies such as evaluation of monoclonal antibody C595 binding to mucine-1 (MUC-1) cell, its purification, size of nanoconjugate and relaxivity measurements. The obtained data showed a powerful relaxations as well as selective MUC-1 antigen binding to the cell. Based on the findings from the present research Gd3+-ALGDG2-C595 nano-probe may be a potential breast molecular imaging and therapeutic agent. However, further investigations by in vivo studies and clinical trials are in the pipeline.
Cite this paper: M. Mirzaei, M. Mohagheghi and D. Shahbazi-Gahrouei, "Synthesis and Development of Gd3+-ALGDG2-C595 as MR Imaging Contrast Agent," Journal of Biomaterials and Nanobiotechnology, Vol. 4 No. 1, 2013, pp. 22-29. doi: 10.4236/jbnb.2013.41004.

[1]   A. L. Baert and K. Sartor, “Medical Radiology Diagnostic Imaging,” Springer, Heidelberg, 2006.

[2]   S. A. Eccles, G. Box, W. Court, J. Sandle and C. J. Dean, “Preclinical Models for the Evaluation of Targeted Therapies of Metastatic Disease,” Cell Biophysics, Vol. 24-25, No. 1-3, 1994, pp. 279-291.

[3]   K. N. Raymond and V. C. Pierre, “Next Generation, High Relaxivity Gadolinium MRI Agents,” Bioconjugate Chemistry, Vol. 16, No. 1, 2005, pp. 3-8. doi:10.1021/bc049817y

[4]   C. J. Mettlin, G. P. Murphy, R. Ho and H. R. Menck, “The National Cancer Data Base Report on Longitudinal Observations on Prostate Cancer,” Cancer, Vol. 77, No. 10, 1996, pp. 2162-2166. doi:10.1002/(SICI)1097-0142(19960515)77:10<2162::AID-CNCR30>3.0.CO;2-R

[5]   C. Galasko, “The Anatomy and Pathways of Skeletal Metastases,” In: L. Weiss and A. H. Gilbert, Eds., Bone Metastases, G. K. Hall, Boston, 1981, pp. 49-63.

[6]   M. S. O’Reilly, L. Holmgren, Y. Shing, C. Chen, R. A. Rosenthal, M. Moses, W. S. Lane, Y. Cao, E. H. Sage and J. Folkman, “Angiostatin: A Novel Angiogenesis Inhibitor That Mediates the Suppression of Metastases by a Lewis Lung Carcinoma,” Cell, Vol. 79, No. 2, 1994, pp. 315-328. doi:10.1016/0092-8674(94)90200-3

[7]   L. Wang, H. Chen, M. H. Pourgholami, J. Beretov, J. Hao, H. Chao, A. C. Perkins, J. H. Kearsley and L. Yong, “Anti-MUC1 Monoclonal Antibody (C595) and Docetaxel Markedly Reduce Tumor Burden and Ascites and Prolong Survival in an in Vivo Ovarian Cancer Model,” Plos One, Vol. 6, No. 9, 2011, e24405. doi:10.1371/journal.pone.0024405

[8]   D. J. Yang, C. G. Kim, N. R. Schechter, A. Azhdarinia, D. F. Yu, C. S. Oh, J. L. Bryant, E. E. Kim and D. A. Podoloff, “Imaging with 99Tcm-ECDG Targeted at the Multifunctional Glucose Transport System: Feasibility Study with Rodents,” Radiology, Vol. 226, 2003, pp. 465-473. doi:10.1148/radiol.2262011811

[9]   C. F. Geraldes and S. Laurent, “Classification and Basic Properties of Contrast Agents for Magnetic Resonance Imaging”, Contrast Media and Molecular Imaging, Vol. 4, No. 1, 2009, pp. 1-23. doi:10.1002/cmmi.265

[10]   I. Haririan, M. S. Alavidjeh, M. R. Khorramizadeh, M. S. Ardestani, Z. Z. Ghane and H. Namazi, “Anionic Linear-Globular Dendrimer-Cis-Platinum (II) Conjugates Promote Cytotoxicity in Vitro against Different Cancer Cell Lines,” International Journal of Nanomedicine, Vol. 5, 2010, pp. 63-75. doi:10.2147/IJN.S8595

[11]   M. S. Alavidjeh, I. Haririan, M. R. Khorramizadeh, Z. Z. Ghane, M. S. Ardestani and H. Namazi, “Anionic Linear-Globular Dendrimers: Biocompatible Hybrid Materials with Potential Uses in Nanomedicine,” Jopurnal of Material Sciences and Material Medicine, Vol. 21, No. 4, 2010, pp. 1121-1133. doi:10.1007/s10856-009-3978-8

[12]   M. Amanlou, S. D. Siadat, S. E. S. Ebrahimi, A. Alavi, M. R. Aghasadeghi, M. S Ardestani, S. Shanehsaz, M. Ghorbani, B. Mehravi, M. S. Alavidjeh, A. Jabbari-Arabzadeh and M. Abbasi, “Gd3+-DTPA-DG: Novel Nanosized Dual Anticancer and Molecular Imaging Agent,” International Journal of Nanomedicine, Vol. 6, 2011, pp. 747-763. doi:10.2147/IJN.S17648

[13]   D. Shahbazi-Gahrouei, “Novel MR Imaging Contrast Agents for Cancer Detection,” Journal of Research in Medical Sciences, Vol. 14, No. 3, 2009, pp. 141-147.

[14]   R. Singh and D. Bandyopadhyay, “MUC-1: A Target Molecule for Cancer Therapy,” Cancer Biology and Therapy, Vol. 6, No. 4, 2007, pp. 481-486. doi:10.4161/cbt.6.4.4201

[15]   D. Shahbazi-Gahrouei, M. Williams, S. Rizvi and B. J. Allen, “In Vivo Studies of Gd-DTPA-Monoclonal Antibody and Gd-Porphyrins: Potential MR Imaging Contrast Agents for Cancer,” Journal of Magnetic Resonance Imaging, Vol. 14, No. 2, 2001, pp. 169-174. doi:10.1002/jmri.1168

[16]   S. M. Cohen, J. D. Xu, E. Radkov, K. N. Raymond, M. Botta, A. Barge and S. Aime, “Syntheses and Relaxation Properties of Mixed Gadolinium Hydroxypyridinonate MRI Contrast Agents,” Inorganic Chemistry, Vol. 39, No. 25, 2000, pp. 5747-5756. doi:10.1021/ic000563b

[17]   S. H. Koenig and R. D. Brown, “NMR Spectroscopy of Cells and Organism,” CRC Press, Boca Raton, 1987, p. 756.

[18]   S. Von Mensdorff-Pouilly, M. M. Gouretvich, P. Kenemans, A. A. Verstraeten, G. J. Van Kamp, et al., “An Enzyme-Linked Immunosorbent Assay for the Measurement of Circulating Antibodies to Polymorphic Epithelial Mucin (MUC-1),” Tumor Biology, Vol. 19, No. 3, 1998, pp. 186-195. doi:10.1159/000030006

[19]   G. Parnaud, S. Tache, G. Peiffer and D. E. Corpet, “Polyethylene-Glycol Suppresses Colon Cancer and Causes Dose-Dependent Regression of Azoxymethane-Induced Aberrant Crypt Foci in Rats,” Cancer Research, Vol. 59, No. 20, 1999, pp. 5143-5147.

[20]   M. Mirzaei, M. A. Mohagheghi, D. Shahbazi-Gahrouei and A. Khatami, “Novel Nanosized Gd3+-ALGD-G2-C595: In Vivo Dual Selective MUC-1 Positive Tumor Molecular MR Imaging and Therapeutic Agent,” Journal of Nanomedicine and Nanotechnology, Vol. 3, No. 147, 2012, pp. 1000147. doi:10.4172/2157-7439.1000147

[21]   S. Giray, T. Bal, A. M. Kartal, S. K?z?lel and C. Erkey, “Controlled Drug Delivery through a Novel PEG Hydrogel Encapsulated Silica Aerogel System,” Journal of Biomedical Materials Research A, Vol. 100, No. 5, 2012, pp. 1307-1315. doi:10.1002/jbm.a.34056

[22]   N. Fischer-Durand, M. Salmain, B. Rudolf, L. Dai, L. Juge, V. Guérineau, O. Laprévote, A. Vessières and G. Jaouen, “Site-Specific Conjugation of Metal Carbonyl Dendrimer to Antibody and Its Use as Detection Reagent in Immunoassay”, Analytical Biochemistry, Vol. 407, No. 2, 2010, pp. 211-219. doi:10.1016/j.ab.2010.08.027

[23]   P. K. Smith, R. I. Krohn, G. T. Hermanson, A. K. Mallia, F. H. Gartner, M. D. Provenzano, E. K. Fujimoto, N. M. Goeke, B. J. Olson and D. C. Klenk, “Measurement of Protein Using Bicinchoninic Acid,” Analytical Biochemistry, Vol. 150, No. 1, 1985, pp. 76-85. doi:10.1016/0003-2697(85)90442-7