title: F-18 Labeled RGD Probes Based on Bioorthogonal Strain-Promoted Click Reaction for PET Imaging.
abstract: A series of fluorine-substituted monomeric and dimeric cRGD peptide derivatives, such as cRGD-ADIBOT-F (ADIBOT = azadibenzocyclooctatriazole), di-cRGD-ADIBOT-F, cRGD-PEG5-ADIBOT-F, and di-cRGD-PEG5-ADIBOT-F, were prepared by strain-promoted alkyne azide cycloaddition (SPAAC) reaction of the corresponding aza-dibenzocyclooctyne (ADIBO) substituted peptides with a fluorinated azide 3. Among these cRGD derivatives, di-cRGD-PEG5-ADIBOT-F had the highest binding affinity in a competitive binding assay compared to other derivatives and even the original cRGDyk. On the basis of the in vitro study results, di-cRGD-PEG5-ADIBOT-(18)F was prepared from a SPAAC reaction with (18)F-labeled azide and subsequent chemo-orthogonal scavenger-assisted separation without high performance liquid chromatography (HPLC) purification in 92% decay-corrected radiochemical yield (dcRCY) with high specific activity for further in vivo positron emission tomography (PET) imaging study. In vivo PET imaging study and biodistribution data showed that this radiotracer allowed successful visualization of tumors with good tumor-to-background contrast and significantly higher tumor uptake compared to other major organs.
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School , Jeonju, Jeonbuk 561-712, Korea.
authors.forename: Hye Lan
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School , Jeonju, Jeonbuk 561-712, Korea.
authors.forename: Kalme
authors.initials: K
authors.lastname: Sachin
authors.affiliation: Department of Chemistry and Chemical Engineering, Inha University , 100 Inha-ro, Nam-gu, Incheon 402-751, Korea.
authors.forename: Hyeon Jin
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Chemistry and Chemical Engineering, Inha University , 100 Inha-ro, Nam-gu, Incheon 402-751, Korea.
authors.forename: Wonsil
authors.initials: W
authors.lastname: Choi
authors.affiliation: Department of Chemistry, Sogang University , Seoul 121-742, Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Chemical Engineering, Inha University , 100 Inha-ro, Nam-gu, Incheon 402-751, Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
keywords: F-18 labeling method; PET molecular imaging; RGD peptide; copper-free click chemistry; fluorine-18; radiopharmaceuticals; tumor angiogenesis