PURPOSE: Radiolabeled Arg-Gly-Asp (RGD) and Ala-Thr-Trp-Leu-Pro-Pro-Arg (ATWLPPR) peptide analogs have received interests for their capability to serve as radiopharmaceuticals for imaging integrin αvβ3 and Neuropilin-1 (NRP-1) positive tumors, respectively. In this study, we developed a RGD-ATWLPPR heterodimeric peptide which contained both RGD and ATWLPPR motifs in one molecular probe. The aim of this study was to investigate the dual receptor-targeting property and tumor diagnostic value of RGD-ATWLPPR heterodimeric peptide labeled with fluorine-18 (F-18). PROCEDURES: A RGD-ATWLPPR heterodimer was synthesized from c(RGDyK) and ATWLPPR through a glutamate linker. The peptide was radiolabeled by reacting the [(18)F]fluoride-aluminum complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The receptor-binding characteristics and tumor-targeting efficacy of [(18)F]FAl-NOTA-RGD-ATWLPPR were tested in vitro and in vivo. RESULTS: RGD-ATWLPPR had affinity for both integrin αvβ3 and NRP-1 in vitro. [(18)F]FAl-NOTA-RGD-ATWLPPR displayed significantly higher tumor uptake than [(18)F]FAl-NOTA-RGD and [(18)F]FAl-NOTA-ATWLPPR, both in vitro and in vivo. The uptake of the F-18 labeled heterodimer by an U87MG tumor was inhibited only partially in the presence of an excess amount of unlabeled RGD or ATWLPPR but was blocked completely in the presence of both RGD and ATWLPPR. Compared with the monomeric RGD and ATWLPPR peptides, [(18)F]FAl-NOTA-RGD-ATWLPPR showed improved in vivo pharmacokinetics, resulting in a more preferable imaging quality. CONCLUSIONS: [(18)F]FAl-NOTA-RGD-ATWLPPR exhibited significantly improved receptor-targeting properties both in vitro and in vivo compared with the F-18 labeled RGD or ATWLPPR monomers. The improved targeting and localization exhibited by the RGD-ATWLPPR heterodimer provide a foundation for further investigations of its applicability in clinical tumor imaging.
PURPOSE: Radiolabeled Arg-Gly-Asp (RGD) and Ala-Thr-Trp-Leu-Pro-Pro-Arg (ATWLPPR) peptide analogs have received interests for their capability to serve as radiopharmaceuticals for imaging integrin αvβ3 and Neuropilin-1 (NRP-1) positive tumors, respectively. In this study, we developed a RGD-ATWLPPR heterodimeric peptide which contained both RGD and ATWLPPR motifs in one molecular probe. The aim of this study was to investigate the dual receptor-targeting property and tumor diagnostic value of RGD-ATWLPPR heterodimeric peptide labeled with fluorine-18 (F-18). PROCEDURES: A RGD-ATWLPPR heterodimer was synthesized from c(RGDyK) and ATWLPPR through a glutamate linker. The peptide was radiolabeled by reacting the [(18)F]fluoride-aluminum complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The receptor-binding characteristics and tumor-targeting efficacy of [(18)F]FAl-NOTA-RGD-ATWLPPR were tested in vitro and in vivo. RESULTS: RGD-ATWLPPR had affinity for both integrin αvβ3 and NRP-1 in vitro. [(18)F]FAl-NOTA-RGD-ATWLPPR displayed significantly higher tumor uptake than [(18)F]FAl-NOTA-RGD and [(18)F]FAl-NOTA-ATWLPPR, both in vitro and in vivo. The uptake of the F-18 labeled heterodimer by an U87MG tumor was inhibited only partially in the presence of an excess amount of unlabeled RGD or ATWLPPR but was blocked completely in the presence of both RGD and ATWLPPR. Compared with the monomeric RGD and ATWLPPR peptides, [(18)F]FAl-NOTA-RGD-ATWLPPR showed improved in vivo pharmacokinetics, resulting in a more preferable imaging quality. CONCLUSIONS: [(18)F]FAl-NOTA-RGD-ATWLPPR exhibited significantly improved receptor-targeting properties both in vitro and in vivo compared with the F-18 labeled RGD or ATWLPPR monomers. The improved targeting and localization exhibited by the RGD-ATWLPPR heterodimer provide a foundation for further investigations of its applicability in clinical tumor imaging.
Authors: Adrian M Jubb; Laura A Strickland; Scot D Liu; Judy Mak; Maike Schmidt; Hartmut Koeppen Journal: J Pathol Date: 2011-10-25 Impact factor: 7.996
Authors: Ahmedin Jemal; Ram C Tiwari; Taylor Murray; Asma Ghafoor; Alicia Samuels; Elizabeth Ward; Eric J Feuer; Michael J Thun Journal: CA Cancer J Clin Date: 2004 Jan-Feb Impact factor: 508.702
Authors: Mariana A Soares; Felipe C O B Teixeira; Miguel Fontes; Ana Lúcia Arêas; Marcelo G Leal; Mauro S G Pavão; Mariana P Stelling Journal: Biomed Res Int Date: 2015-10-19 Impact factor: 3.411