Preparation and evaluation of 99mTc-labeled cyclic arginine-glycine-aspartate (RGD) peptide for integrin targeting.
Technetium coordination chemistry has been a subject of interest in the development of radiopharmaceuticals, especially imaging radiotracers. Due to the extensive work done on developing chelates for (99m)Tc, various chelators have been investigated and applied to radiopharmceuticals. Previous studies on the coordination chemistry of the [(99m)Tc=O] core have established peptide-derived sequences as effective chelating ligands. These observations led to the design of tetradentate ligands derived from amino acid sequences. Such amino acid sequences provide a tetradentate coordination site for chelation to the radionuclide and an effective functional group for conjugation to biomolecules using conventional solid-phase synthetic routes. A derivative of a novel tripeptide chelating sequence, Pro-Gly-Cys (PGC) has been developed where it is possible to form stable technetium complexes with the [(99m)Tc=O] via N(3)S(1) tetradentate coordination core that serves this function and can be readily incorporated into biomolecules using solid-phase synthesis techniques. As a model system, the RGD peptide was selected which has been well known to target the integrin receptor for angiogenesis and tumor imaging agents. The results of in vivo studies with these novel radiolabeled compounds in tumor xenografts demonstrated a distribution in tumor targeting and other organs, such as kidney, liver and intestines.
Lee
Dong-Eun
DE
Radioisotope Research Division, Basic Science and Technology Department, Korea Atomic Energy Research Institute, Daejon 305-353, Republic of Korea.
Hong
Young-Don
YD
Choi
Kang-Hyuk
KH
Lee
So-Young
SY
Park
Pil-Hoon
PH
Choi
Sun-Ju
SJ
D000818:Animals; D016503:Drug Delivery Systems; D016023:Integrins / Q000032:analysis* / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis; D010456:Peptides, Cyclic / Q000138:chemical synthesis; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D013667:Technetium; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
D016023:Integrins; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C507169:cyclic arginine-glycine-aspartic acid peptide; D013667:Technetium