title: A novel concept of radiosynthesis of a (99m)Tc-labeled dimeric RGD peptide as a potential radiotracer for tumor imaging.
abstract: Radiolabeled Arg-Gly-Asp (RGD) peptides are promising agents for non invasive imaging of αvβ3 expression in malignant tumors. The integrin αvβ3 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 (99m)Tc labeled dimeric RGD derivative using a RGD monomer and [(99m)TcN](+2) intermediate. The dithiocarbamate derivative of cyclic RGD peptide G3-c(RGDfK) (G3=Gly-Gly-Gly, f=Phe, K=Lys) was synthesized and radiolabeled with [(99m)TcN](+2) intermediate to form the (99m)TcN-[G3-c(RGDfK)]2 complex in high yield (∼98%). Biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed good tumor uptake [4.61±0.04% IA/g at 30min 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.
authors: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors: Sweety
authors: S
authors: Mittal
authors: Mohini
authors: M
authors: Bhadwal
authors: Sudipta
authors: S
authors: Chakraborty
authors: H D
authors: HD
authors: Sarma
authors: Sharmila
authors: S
authors: Banerjee
authors: M R A
authors: MR
authors: Pillai
mesh_terms: D000818:Animals; D019281:Dimerization; D006207:Half-Life; D039302:Integrin alphaVbeta3 / Q000737:chemistry / Q000378:metabolism; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000737:chemistry*; D011485:Protein Binding; D011859:Radiography; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D013859:Thiocarbamates / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013859:Thiocarbamates; C047981:arginyl-glycyl-aspartic acid