Radiolabeling and evaluation of 188Re-RGD as an agent for αvβ3 receptor expression

RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE

Radiolabeling and evaluation of ¹⁸⁸Re-RGD as an agent for α_vβ₃ receptor expression

Yufei MA，

Junfeng YU，

Cheng WANG，

Hua SHEN，

Hua WU

Nuclear Science and Techniques

Vol.23, No.1

pp.47-51

Published in print 20 Feb 2012

DOI：10.13538/j.1001-8042/nst.23.47-51

33000

Integrin α_vβ₃, a cell adhesion molecule, plays a key role in angiogenesis and tumor cell metastasis and is therefore an important target for new therapeutic and diagnostic strategies. Since RGD bind to α_vβ₃ particularly, a lot of RGD containing peptides were radiolabeled and evaluated as imaging or therapeutic agents. In this study, a new ¹⁸⁸Re-RGD peptide analog was synthesized and characterized. Within 30 min, the ¹⁸⁸Re-H-E[c(RGDyK)]₂ was obtained in radiochemical purity of better than 95%. The His-E[c(RGDyK)]₂ had a good integrin-binding affinity (50% inhibitiory concentracer (IC₅₀=46.5×10^–9 nm) and exhibited active accumulation (7.20±1.06) in S180 tumor. Because of relatively fast washout in blood and normal tissues, the target/non-target ratio was high. Further experiments to improve the tumor targeting efficacy and in vivo kinetic profiles are in progress towards developing it into a promising radio agent.

fac-[188Re(H2O)3(CO)3]+RGD peptideIntegrinαvβ3

References

[1]

Folkman J. N Engl J Med, 1971, 285: 1182-1186.

[2]

Bergers G, Benjamin L E. Nat Rev Cancer, 2003, 3: 401-410.

[3]

Brooks P C. Eur J Cancer, 1996, 32A: 2423-2429.

[4]

Hood J D, Cheresh D A. Nat Rev Cancer, 2002, 2: 91-100.

[5]

Jin H, Varner J. Br J Cancer, 2004, 90: 561-565.

[6]

Ambros J B, Markus S. Cancer Metastasis Rev, 2008, 27: 631-644.

[7]

Xiong J P, Stehle T, Zhang R, et al. Science, 2002, 296: 151-155.

[8]

Plow E F, Haas T A, Zhang L, et al. J Biol Chem, 2000, 275: 21785-21788.

[9]

Ingrid-Dijkgraaf , Kruijtzer A W J, Shuang L, et al. Eur J Nucl Med Mol Imaging, 2007, 34: 267-273.

[10]

Zhang X Z, Chen X. Appl Radiat Isotopes, 2007, 65: 70-78.

[11]

Chen X, Tohme M, Park R, et al. Mol Imaging, 2004, 3: 96-104.

[12]

Zhang X, Xiong Z, Wu Y, et al. J Nucl Med, 2006, 47: 113-121.

[13]

Luo T Y, Tang I C, Wu Y L, et al. Nucl Med Biology, 2009, 36: 81-88.

[14]

Yu J F, Häfeli U O, Xia J Y, et al. Nuclear Medicine Communications, 2005, 26: 453-458.