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

Radiolabeling and evaluation of 188 Re-RGD as an agent for α v β 3 receptor expression 1 first-author 2 2 2 1 corresp Corresponding author. E-mail address: wuhua1023@163.com Corresponding author. E-mail address: wuhua1023@163.com wuhua1023@163.com Department of Nuclear Medicine, the First affiliataed Hospital, Xiamen University, 55 Zhenhai Rd., Xiamen 361003, China Department of Nuclear Medicine, the First affiliataed Hospital, Xiamen University, 55 Zhenhai Rd., Xiamen 361003, China Centre of Radiopharmaceutical Research, Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai 201800, China Centre of Radiopharmaceutical Research, Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai 201800, China Integrin α v β 3 , 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 v β 3 particularly, a lot of RGD containing peptides were radiolabeled and evaluated as imaging or therapeutic agents. In this study, a new 188 Re-RGD peptide analog was synthesized and characterized. Within 30 min, the 188 Re-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 (IC 50 =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 -[ 188 Re(H 2 O) 3 (CO) 3 ] + RGD peptide Integrinα v β 3 References Folkman J . N Engl J Med , 1971 , 285 : 1182 - 1186 . N Engl J Med Bergers G , Benjamin L E . Nat Rev Cancer , 2003 , 3 : 401 - 410 . Nat Rev Cancer Brooks P C . Eur J Cancer , 1996 , 32A : 2423 - 2429 . Eur J Cancer Hood J D , Cheresh D A . Nat Rev Cancer , 2002 , 2 : 91 - 100 . Nat Rev Cancer Jin H , Varner J . Br J Cancer , 2004 , 90 : 561 - 565 . Br J Cancer Ambros J B , Markus S . Cancer Metastasis Rev , 2008 , 27 : 631 - 644 . Cancer Metastasis Rev Xiong J P , Stehle T , Zhang R , et al . Science , 2002 , 296 : 151 - 155 . Science Plow E F , Haas T A , Zhang L , et al . J Biol Chem , 2000 , 275 : 21785 - 21788 . J Biol Chem Ingrid-Dijkgraaf , Kruijtzer A W J , Shuang L , et al . Eur J Nucl Med Mol Imaging , 2007 , 34 : 267 - 273 . Eur J Nucl Med Mol Imaging Zhang X Z , Chen X . Appl Radiat Isotopes , 2007 , 65 : 70 - 78 . Appl Radiat Isotopes Chen X , Tohme M , Park R , et al . Mol Imaging , 2004 , 3 : 96 - 104 . Mol Imaging Zhang X , Xiong Z , Wu Y , et al . J Nucl Med , 2006 , 47 : 113 - 121 . J Nucl Med Luo T Y , Tang I C , Wu Y L , et al . Nucl Med Biology , 2009 , 36 : 81 - 88 . Nucl Med Biology Yu J F , Häfeli U O , Xia J Y , et al . Nuclear Medicine Communications , 2005 , 26 : 453 - 458 . Nuclear Medicine Communications 10.13538/j.1001-8042/nst.23.47-51 Supported by Nature Science Foundation of China under Contract NO.81101066 2011-02-24 2012-02-20 2021-01-19 2012 Nuclear Science and Techniques 01 23