Preparation and Bioevaluation of DOTA-Cyclic RGD Peptide Dimer Labeled with 68Ga

Authors: Archana Mukherjee, Aruna Korde, Sudipta Chakraborty, H. D. Sarma, Grace Samuel, M. R. A. Pillai

Abstract:

Radiolabeled cyclic RGD peptides targeting integrin αvβ3 are reported as promising agents for the early diagnosis of metastatic tumors. With an aim to improve tumor uptake and retention of the peptide, cyclic RGD peptide dimer E[c (RGDfK)] 2 (E = Glutamic acid, f = phenyl alanine, K = lysine) coupled to the bifunctional chelator DOTA was custom synthesized and radiolabelled with 68Ga. Radiolabelling of cyclic RGD peptide dimer with 68Ga was carried out using HEPES buffer and biological evaluation of the complex was done in nude mice bearing HT29 tumors.

Keywords: 68Ga peptides, Angiogenesis imaging, Cyclic RGD peptides, PET Imaging.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1072996

References:

[1] R. Haubner, "╬▒vβ3-integrin imaging: a new approach to characterize angiogenesis?", Eur J Nucl Med Mol Imaging vol. 33, pp. S54-S63, 2006.
[2] P.A.Knetsch, M.Petrik, C.M. Griessinger, C. Rangger, M. Fani, C. Kesenheimer, E. V. Guggenberg,& B.J.Pichler, I.Virgolini, C. Decristoforo,R.Haubner, "(68Ga)NODAGA-RGD for imaging ╬▒vβ3 integrin expression", Eur J Nucl Med Mol Imaging, vol. 38, pp. 1303- 1312, 2011.
[3] S. Liu, "Radiolabeled Cyclic RGD Peptides as Integrin ╬▒vβ3-Targeted Radiotracers: Maximizing Binding Affinity via Bivalency" Bioconjugate Chem., vol. 20 (12), pp. 2199-2213, 2009.
[4] I. Dijkgraaf, J. A. W. Kruijtzer, S. Liu, A. C. Soede, W.J. G. Oyen, F.H. M. Corstens, R.M.J. Liskamp, O. C. Boerman, "Improved targeting of the ╬▒vβ3 integrin by multimerisation of RGD peptides" Eur J Nucl Med Mol Imaging, vol. 34, pp. 267-273, 2007.
[5] M. Brom, L. Joosten, W. J.G. Oyen, M. Gotthardt, O.C. Boerman, "Improved labelling of DTPA- and DOTA conjugated peptides and antibodies with 111In in HEPES and MES buffer", EJNMMI Research vol.2, pp.4, 2012
[6] S. Chakraborty, R.Chakravarty, H.D.Sarma, A. Dash, M.R.A.Pillai, "The Practicality of Nanoceria-PAN-Based (68) Ge/ (68) Ga Generator Toward Preparation of (68) Ga-Labeled Cyclic RGD Dimer as a Potential PET Radiotracer for Tumor Imaging", Cancer Biother Radiopharm, (In press) 2013.