A novel concept of radiosynthesis of a Tc-99m-labeled dimeric RGD peptide as a potential radiotracer for tumor imaging

作者：Mittal Sweety; Bhadwal Mohini; Chakraborty Sudipta; Sarma H D; Banerjee Sharmila^*; Pillai M R A

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(6): 1808-1812.

DOI：10.1016/j.bmcl.2013.01.036

• Angiogenesis
• Integrin alpha(v)beta(3)
• RGD
• [(TcN)-Tc-99m](+2) precursor complex

Radiolabeled Arg-Gly-Asp (RGD) peptides are promising agents for non invasive imaging of alpha(v)beta(3) expression in malignant tumors. The integrin alpha(v)beta(3) binding affinity and consequent tumor uptake could be improved when a dimeric RGD peptide is used as the targeting moiety instead of a monomer. Towards this, a novel approach was envisaged to synthesize a Tc-99m labeled dimeric RGD derivative using a RGD monomer and [(TcN)-Tc-99m](+2) intermediate. The dithiocarbamate derivative of cyclic RGD peptide G(3)-c(RGDfK) (G(3) = Gly-Gly-Gly, f = Phe, K = Lys) was synthesized and radiolabeled with [(TcN)-Tc-99m](+2) intermediate to form the (TcN)-Tc-99m-[G(3)-c(RGDfK)](2) complex in high yield (similar to 98%). Biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed good tumor uptake [4.61 +/- 0.04% IA/g at 30 min post-injection] with fast clearance of the activity from non-target organs/tissue. Scintigraphic imaging studies showed visible accumulation of activity in the tumor with appreciable target to background ratio.

• 出版日期2013-3-15