Development of a bifunctional chelating agent containing isothiocyanate residue for one step F-18 labeling of peptides and application for RGD labeling.
We report herein a novel isothiocyanate active ligand for fluorine-18 labeling prepared by four step synthesis. It can be conjugated to a target molecule containing an amino functional group under weak basic conditions by way of thiourea bond formation. We explored the application of synthesized ligand by conjugating to well known α(v)β(3) integrin targeting peptide, c(RGDyK). The conjugated peptide showed good radiochemical yield and efficiency with an excellent radiochemical purity (97.1 ± 1.2%) in a short reaction time (10 min). Labeled peptide showed excellent in vitro and in vivo stability (>95%). α(v)β(3) integrin specific tumor uptake was observed both in biodistribution and small animal microPET studies on α(v)β(3)-positive U87MG (human glioma cells) xenograft bearing mice. In general, successful application of synthesized ligand for labeling of RGD peptide could facilitate the possibility of using this ligand for labeling peptides containing an amino functional group.
Department of Nuclear Medicine, Department of Radiation Applied Life Science and Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Dinesh
D
Shetty
Jae Min
JM
Jeong
Young Ju
YJ
Kim
Ji Youn
JY
Lee
Lathika
L
Hoigebazar
Yun-Sang
YS
Lee
Dong Soo
DS
Lee
June-Key
JK
Chung
D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D005910:Glioma / Q000000981:diagnostic imaging*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D017879:Isothiocyanates / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D049268:Positron-Emission Tomography
D002614:Chelating Agents; D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D017879:Isothiocyanates; D009842:Oligopeptides; C037152:isothiocyanic acid; C047981:arginyl-glycyl-aspartic acid